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Increasing Understanding (increasing + understanding)

Distribution by Scientific Domains
Medical Sciences66%
Life Sciences33%

Selected Abstracts

Cytoprotection of beta cells: rational gene transfer strategies

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2006
Cillian McCabe
Abstract Gene transfer to pancreatic islets may prove useful in preventing islet cell destruction and prolonging islet graft survival after transplantation in patients with type 1 diabetes mellitus (T1DM). Potentially, a host of therapeutically relevant transgenes may be incorporated into an appropriate gene delivery vehicle and used for islet modification. An increasing understanding of the molecular pathogenesis of immune-mediated beta cell death has served to highlight molecules which have become suitable candidates for promoting islet cell survival in the face of oxidative stress. This review aims to give an overview of some conventional gene transfer strategies aimed at promoting islet cell survival in the face of cytokine onslaught. These strategies target three aspects of islet cell physiology: redox status and antioxidant defence, anti-apoptotic gene expression and mediators of cytokine signal transduction pathways. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Intrinsic properties of human and murine memory B cells

IMMUNOLOGICAL REVIEWS, Issue 1 2006
Shannon M. Anderson
Summary:, The central question of how the immune system responds in a qualitatively and quantitatively better way upon re-exposure to a pathogen is largely unanswered. Both the increased frequency of antigen-specific memory cells and the intrinsic properties that memory cells acquire after antigen experience could contribute to the faster and more robust responses seen after repeated exposure to antigen. In the case of the memory B-cell response, it has been difficult to discern the individual contributions of these two effects. However, because of recent advances in identifying memory B cells, there is an increasing understanding of the intrinsic properties of these cells. The current insights into the unique properties of memory B cells and the progress that has been made in understanding how these affect secondary responses in both the human and the mouse systems are discussed. In addition, we compare the various advantages and disadvantages inherent in each of these systems, in terms of studying the intrinsic properties of memory B cells, and introduce the details of the system that we have developed using conventional heavy chain transgenic (Tgic) mice, which addresses some of the drawbacks of traditional memory models. [source]

Role of hypoxia in the hallmarks of human cancer

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009
Kai Ruan
Abstract Hypoxia has been recognized as one of the fundamentally important features of solid tumors and plays a critical role in various cellular and physiologic events, including cell proliferation, survival, angiogenesis, immunosurveillance, metabolism, as well as tumor invasion and metastasis. These responses to hypoxia are at least partially orchestrated by activation of the hypoxia-inducible factors (HIFs). HIF-1 is a key regulator of the response of mammalian cells to oxygen deprivation and plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Hypoxia and overexpression of HIF-1 have been associated with radiation therapy and chemotherapy resistance, an increased risk of invasion and metastasis, and a poor clinical prognosis of solid tumors. The discovery of HIF-1 signaling has led to a rapidly increasing understanding of the complex mechanisms involved in tumor hypoxia and has helped greatly in screening novel anticancer agents. In this review, we will first introduce the cellular responses to hypoxia and HIF-1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers. J. Cell. Biochem. 107: 1053,1062, 2009. © 2009 Wiley-Liss, Inc. [source]

Review article: steroid resistance in inflammatory bowel disease , mechanisms and therapeutic strategies

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007
T. J. CREED
Summary Background Steroid resistance in inflammatory bowel disease presents a difficult clinical challenge. The advent of biological therapies coupled with an increasing understanding of the pathogenesis of inflammatory bowel disease has provided new therapeutic options. Methods We review the available literature of the mechanisms behind steroid resistance. In addition, we outline some of the options available for treating those patients who fail to respond adequately to glucocorticoids. Results Approximately 30% of patients prescribed glucocorticoids will not achieve clinical remission. Many such patients are offered immunosuppressive or, recently, biological agents. However, these agents are ineffective in a large proportion of patients. Immunosuppressive agents only bring 40,60% of patients into remission, and biological agents typically induce remission in just 40% of patients. In this review, the possible explanations for glucocorticoid resistance are discussed. Recent evidence suggests that in many patients it is mediated by interleukin-2. Basiliximab, a biological agent that interrupts interleukin-2 signalling, has shown significant benefit in early clinical studies. Conclusions Patients who fail to respond to steroid therapy should have alternative agents introduced in a timely fashion. Steroid refractory inflammatory bowel disease remains a difficult condition to treat, but new therapies and managements are emerging. [source]

Antiepileptic drug discovery: lessons from the past and future challenges

ACTA NEUROLOGICA SCANDINAVICA, Issue 2005
H. Klitgaard
Historically, most antiepileptic drugs (AEDs) have been discovered either by serendipity, or the screening of compounds using acute seizure models. However, an increasing understanding of the molecular mechanisms underlying epileptogenesis has led to more rational approaches to drug discovery, which have focused on either enhancing inhibitory , -amino butyric acid (GABA)-ergic, or antagonizing excitatory glutamatergic, neurotransmission. Unfortunately, AEDs generated using such strategies have poor efficacy and safety profiles, as they interfere with normal cell processes, while ignoring the complex underlying pathophysiology of epilepsy. Recently, however, the use of new epilepsy models has led to the discovery of levetiracetam, an AED with a truly unique mechanism of action, devoid of anticonvulsant activity in normal animals, but with potent seizure suppression in genetic and kindled chronic epilepsy models, and an unusually high safety margin. The recent identification of brivaracetam and seletracetam, which optimize this unique mechanism of action, may further improve the medical management of epilepsy. The experience with levetiracetam, brivaracetam and seletracetam reveals that new experimental epilepsy models can detect AEDs possessing a unique mechanism of action and thereby target the future challenge of providing clinicians novel additions to the current armamentarium of AEDs. [source]

Reviewing the vascular supply of the anterior abdominal wall: Redefining anatomy for increasingly refined surgery

CLINICAL ANATOMY, Issue 2 2008
W.M. Rozen
Abstract The abdominal wall integument is becoming the standard donor tissue for postmastectomy breast reconstruction, with its vascular supply of key importance to the reconstructive surgeon. Refinements in tissue transfer, from pedicled to free flaps and musculocutaneous to perforator flaps, have required increasing understanding of finer levels of this vascular anatomy. The widespread utilization of the deep inferior epigastric artery (DIEA) perforator flap, particularly for breast reconstruction, has rekindled clinical interest in further levels of anatomical detail, in particular the location and course of the musculocutaneous perforators of the DIEA. Advances in operative techniques, and anatomical and imaging technologies, have facilitated an increase in this understanding. The current review comprises an appraisal of both the anatomical and clinical literature, with a view to highlighting the key anatomical features of the abdominal wall vasculature as related to reconstructive flaps. Clin. Anat. 21:89,98, 2008. © 2008 Wiley-Liss, Inc. [source]