Abstract:
:Of the dideoxynucleosides described to date, the purine analogues ddA and ddI have exhibited very favorable therapeutic ratios in vitro. ddI is presently undergoing extensive phase I-II clinical trials. Whereas the action of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) is usually to convert a given analogue of Ado to an inactive or less active form, ddI appears to retain the same biological activity as that of the parent ddA. An explanation for these observations was possible when we found that ddI (1) underwent only a slow cleavage to hypoxanthine through the action of PNP and (2) accumulated the same active antiviral metabolite (i.e., ddATP) as ddA in human lymphoid cells. The use of human lymphoid cells with deficiencies in cellular nucleoside kinases and of inhibitors of pathways of nucleotide metabolism have also revealed new aspects of dideoxypurine metabolism in human lymphoid cells, including the identification of a salvage pathway (phosphotransferase/5'-nucleotide pathway) by which ddA/ddI may be metabolized preferentially to the active nucleotide. The effectiveness of ddA and ddI as orally administered antiviral agents may be limited by their susceptibility to acid hydrolysis and the low efficiency for nucleotide conversion in human lymphoid cells. The presence of a fluorine atom in the arabinose configuration on C-2 confers resistance to solvolysis and renders the analogue less susceptible to enzymatic deamination and resistant to phosphorylytic cleavage by PNP. In addition, human lymphoid cells accumulated several fold higher levels of the putative active triphosphate, 2'-F-dd-ara-ATP, than those of ddA or ddI. This increased accumulation of the analogue triphosphate could be accounted for by a more direct conversion of 2'-F-dd-ara-A by a direct phosphorylation through dCyd kinase than ddA. Thus, a single substitution with fluorine at the 2' "up" position of the sugar moiety of ddA markedly improves several biochemical properties relating to dideoxynucleotide accumulation in human lymphoid cells. Whether there are significant alterations of other biochemical properties, such as the ability of the analogue triphosphate to interact with the target enzyme reverse transcriptase, has not yet been determined. Thus, a definitive resolution of the relative merit of ddA/ddI and its 2'-fluoro-arabinosyl analogue is not yet possible on the basis of the studies described here.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Fridland A,Johnson MA,Cooney DA,Ahluwalia G,Marquez VE,Driscoll JS,Johns DGdoi
10.1111/j.1749-6632.1990.tb17841.xsubject
Has Abstractpub_date
1990-01-01 00:00:00pages
205-16eissn
0077-8923issn
1749-6632journal_volume
616pub_type
杂志文章abstract::Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. Fractalkine, a CX3C/chemokine (CX3CL1), mediates monocytes-macrophage infiltration in activated endothelium, suggesting its specific role in atherosclerosis-related inflammation. In this study, we evaluate the following in early RA patients: the...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1381.004
更新日期:2007-06-01 00:00:00
abstract::Social behavior in most human societies is characterized by the following of moral rules explicitly justified by religious belief systems. These systems constitute the diverse domain of human sacred values. Supernatural entities as founders or warranty of moral principles may be seen as a form of "conversation stopper...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04603.x
更新日期:2009-06-01 00:00:00
abstract::The asymmetric inheritance of NUMB during mitosis determines future daughter cell fates in multiple model organisms. NUMB asymmetric inheritance has also been postulated for hematopoietic stem cell (HSC) divisions but remained controversial until recently. To reconcile conflicting reports, we revisited the evidence fo...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/nyas.14284
更新日期:2020-04-01 00:00:00
abstract::Leukocyte trafficking from the blood stream to tissues is essential for continuous surveillance of foreign antigens. This dynamic process, designated as the leukocyte adhesion cascade, involves distinct steps. In leukocyte adhesion deficiency (LAD) I the firm adhesion of leukocyte to the endothelium is defective, due ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2011.06389.x
更新日期:2012-02-01 00:00:00
abstract::Tight and adherens junctions play critical roles in the barrier, adhesion, and signaling functions of epithelial and endothelial cells. How the molecular organization of these junctions is tuned to the widely diverse physiological requirements of each tissue type is not well understood. Here, we address this question ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/nyas.13391
更新日期:2017-10-01 00:00:00
abstract::Morphogenesis in the animal kingdom is closely coupled with the intracellular synthesis and the extracellular deposition of collagen. These morphogenetically important events involve multiple steps which begin in compartments inside the cell and continue in compartments outside the cell. The movement of matrix compone...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1985.tb51173.x
更新日期:1985-01-01 00:00:00
abstract::Drug addiction is a chronic relapsing brain disorder characterized by neurobiological changes that lead to a compulsion to take a drug with loss of control over drug intake. The hypothesis outlined here is that knowledge of the neurochemical systems involved in the transition from drug use to the compulsive use of add...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2000.tb06682.x
更新日期:2000-01-01 00:00:00
abstract::The clinical significance of lymphocytic esophagitis (LyE), which is characterized by the prominence of peripapillary intraepithelial lymphocytes (IELs) without significant granulocytosis, remains poorly understood. During the last few years, plausible clinical correlates and novel approaches for stratification of LyE...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13260
更新日期:2016-10-01 00:00:00
abstract::Until now, neoadjuvant therapy plus surgical resection of the primary tumor and potential metastatic lymph nodes (LNs) has been the current optimal treatment for locally advanced thoracic esophageal cancer (EC). LN metastasis is one of the most negative prognostic factors for thoracic esophageal squamous cell carcinom...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.14427
更新日期:2020-12-01 00:00:00
abstract::This review aims to discuss the neurophysiology of the esophagus and new methods to assess esophageal nociception. Pain and other symptoms can be caused by diseases in the mucosa or muscular or sphincter dysfunction, together with abnormal pain processing, either in the peripheral or central nervous systems. Therefore...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13175
更新日期:2016-09-01 00:00:00
abstract::Mouse models with targeted deletion of the genes encoding the enzyme 25-hydroxyvitamin D 1alpha-hydroxylase [1alpha(OH)ase], and the vitamin D receptor (VDR), have provided considerable insight into the regulation of mineral and skeletal physiology by 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. Dietary manipulation induce...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2009.05226.x
更新日期:2010-03-01 00:00:00
abstract::The 21st century offers new advances in diagnostic procedures and protocols in the management of esophageal diseases. This review highlights the most recent advances in esophageal diagnostic technologies, including clinical applications of novel endoscopic devices, such as ultrathin endoscopy and confocal laser endomi...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13255
更新日期:2016-09-01 00:00:00
abstract::This review focuses on the importance of bradykinin in myocardial preservation during ischemic arrest. Bradykinin is released from the heart spontaneously in response to ischemic stress, which may be viewed as a survival signal of the heart against ischemia. Bradykinin appears to function as a signaling molecule by co...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1999.tb09244.x
更新日期:1999-06-30 00:00:00
abstract::Neuropsychiatric disorders (i.e., mood disorders and schizophrenia) and inflammation are closely intertwined, and possibly powering each other in a bidirectional loop. Depression facilitates inflammatory reactions and inflammation promotes depression and other neuropsychiatric disorders. Patients with neuropsychiatric...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13712
更新日期:2019-02-01 00:00:00
abstract::In the United States, some 80,000 commercial and industrial chemicals are now in use of which over 30,000 are produced or used in the Great Lakes region. Thus, the environmental quality within the Great Lakes basin has been compromised particularly with respect to persistent toxic substances (PTS). Information derived...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1371.028
更新日期:2006-09-01 00:00:00
abstract::We have been interested in the consequences of foreign DNA insertion into established mammalian genomes and have initially studied this problem in adenovirus type 12 (Ad12)-transformed cells or in Ad12-induced hamster tumors. Since integrates are frequently methylated de novo, it appears that they might be modified by...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2001.tb03896.x
更新日期:2001-09-01 00:00:00
abstract::Pregnancy rates among adolescents have not decreased over the last 10 years, despite numerous efforts. To solve this important health problem, the major strategy recommended is to encourage contraceptive use among sexually active teenagers. An important means of obtaining this is by promoting methods that are not depe...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1749-6632.1997.tb52174.x
更新日期:1997-06-17 00:00:00
abstract::One in 12 people worldwide suffers from diabetes and more than 90% of affected adult individuals are diagnosed with type 2 diabetes mellitus (T2DM). Obesity adds to the personal risk to develop T2DM, and both metabolic diseases are rampantly increasing worldwide. Over recent years, primary cilia have moved into the fo...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13216
更新日期:2017-03-01 00:00:00
abstract::A male factor is implicated in about 50% of couples treated with advanced assisted reproductive techniques (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). An important function of spermatozoa is to deliver the paternal genome to the oocyte. However, neither the routine testing of male fertil...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1434.021
更新日期:2008-04-01 00:00:00
abstract::Multiple subsets of nociceptive, parasympathetic, and sympathetic nerves innervate human nasal mucosa. These play carefully coordinated roles in regulating glandular, vascular, and other processes. These functions are vital for cleaning and humidifying ambient air before it is inhaled into the lungs. The recent identi...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04481.x
更新日期:2009-07-01 00:00:00
abstract::This study aimed to assess the value of different DXA and BIA models for predicting muscle volume in mid-thigh segments obtained by MRI. Three DXA models were used: in model A, muscle was taken to be equivalent to fat-free soft tissue; in model B the thigh segment was divided into its constituent tissues using fixed a...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2000.tb06471.x
更新日期:2000-05-01 00:00:00
abstract::Since the publication of Heinz Kohut's last book in 1984, "self psychology" has become much more diverse in its perspectives and even fragmented in its applications. Perhaps due in large part to Kohut's own inconsistencies and lack of clarity on certain major points of theory and technique, self psychology currently l...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2008.04340.x
更新日期:2009-04-01 00:00:00
abstract::Acute viral infection of humans induces virus-specific serum antibody production that often persists for decades. To better understand the nature of this long-term antiviral antibody response, we studied antiviral antibody production of mice acutely infected with lymphocytic choriomeningitis virus (LCMV). Although thi...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1996.tb52958.x
更新日期:1996-10-25 00:00:00
abstract::The homeostasis of skeletal tissues requires tight regulation of a variety of signaling pathways, and the onset and progression of skeletal diseases are often caused by signaling abnormalities. MicroRNAs (miRNAs) are short noncoding RNA molecules that have emerged as a new dimension of gene regulation. MiRNAs have bee...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13206
更新日期:2016-11-01 00:00:00
abstract::Young songbirds memorize a tutor song and use the memory trace as a template to shape their own song by auditory feedback. Major issues in birdsong research include the neural sites and mechanisms for song memory and auditory feedback. The brain song control system contains neurons with both premotor and auditory func...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1298.010
更新日期:2004-06-01 00:00:00
abstract::These initial studies show that deregulated expression of ALG7 affects diverse cellular functions crucial to development, including proliferation, differentiation, and morphogenesis. Furthermore, the data suggest multiple genetic targets for ALG7 and provide the basis for future dissection of these developmentally rel...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1998.tb09648.x
更新日期:1998-04-15 00:00:00
abstract::Rapidly industrializing India is described by the International Monetary Fund as a young, disciplined, and vibrant economy with a projected growth of 6.7% for 2005. The total workforce of 397 million has only 7% of workers employed in the organized sector with construction, where asbestos exposure is prevalent, employ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1371.072
更新日期:2006-09-01 00:00:00
abstract::This study investigated self-recognition in point-light displays depicting actions performed in synchrony with music. Participants were recorded executing three different actions (dancing, walking, and clapping) and were subsequently required to identify the agent (self versus other) from point-light displays with or ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04773.x
更新日期:2009-07-01 00:00:00
abstract::Colorectal cancer is the third most frequent fatal malignant neoplasm in the United States and is expected to cause significant morbidity and mortality. The recent recall of cyclooxygenase-2 inhibitors from clinical trials highlights the need to develop other agents for cancer chemoprevention trials. Intervention stra...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1339.016
更新日期:2005-11-01 00:00:00
abstract::In common marmoset monkeys (Callithrix jacchus, order Primates), infants aged 2-28 days were deprived of parental care for 30-120 min/day in order to investigate the long-term effects of this neglect-stress model on affect and cognition in a primate species. Basal morning levels of urinary cortisol across the first ye...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1314.030
更新日期:2004-12-01 00:00:00