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Human Investigations (human + investigation)
Selected AbstractsSome interfaces of dendritic cell biologyAPMIS, Issue 7-8 2003RALPH M. STEINMAN The field of dendritic cell (DC) biology is robust, with several new approaches to analyze their role in vivo and many newly recognized functions in the control of immunity and tolerance. There also is no shortage of mysteries and challenges. To introduce this volume, I would like to summarize four interfaces of DC research with other lines of investigation and highlight some current issues. One interface is with hematopoiesis. DCs constitute a distinct lineage of white blood cell development with some unique features, such as their origin from both lymphoid and myeloid progenitors, the existence of several distinct subsets, and an important final stage of differentiation termed "maturation," which occurs in response to inflammation and infection, and is pivotal for determining the subsequent immune response. A second interface is with lymphocyte biology. DCs are now known to influence many different classes of lymphocytes (B, NK, NKT) and many types of T cell responses (Th1/Th2, regulatory T cells, peripheral T cell deletion), not just the initial priming or induction of T cell-mediated immunity, which was the first function to be uncovered. DCs are sentinels, controlling many of the afferent or inductive limbs of immune function, alerting the immune system and controlling its early decisions. A third interface is with cell biology. This is a critical discipline to understand at the subcellular and molecular levels the distinct capacities of DCs to handle antigens, to move about the body in a directed way, to bind and activate lymphocytes, and to exert many quality controls on the type of responses, for both tolerance and immunity. A fourth interface is with medicine. Here DCs are providing new approaches to disease pathogenesis and therapy. This interface is perhaps the most demanding, because it requires research with humans. Human research currently is being slowed by the need to deal with many challenges in the design of such studies, and the need to excite, attract and support the young scientists who are essential to move human investigation forward. Nonetheless, DCs are providing new opportunities to study patients and the many clinical conditions that involve the immune system. [source] Recent Insights into Carotid Baroreflex Function in Humans Using the Variable Pressure Neck ChamberEXPERIMENTAL PHYSIOLOGY, Issue 6 2003Paul J. Fadel The variable pressure neck chamber has provided an invaluable research tool for the non-invasive assessment of carotid baroreflex (CBR) function in human investigations. The ability to construct complete stimulus-response curves and define specific parameters of the reflex function curve permits statistical comparisons of baroreflex function between different experimental conditions, such as rest and exercise. Results have convincingly indicated that the CBR stimulus-response curve is reset during exercise in an intensity-dependent manner to functionally operate around the prevailing pressure elicited by the exercise workload. Furthermore, both at rest and during exercise, alterations in stroke volume do not contribute importantly to the maintenance of arterial blood pressure by the carotid baroreceptors, and therefore, any reflex-induced changes in cardiac output (Q) are the result of CBR-mediated changes in heart rate. However, more importantly, the CBR-induced changes in mean arterial pressure (MAP) are primarily mediated by alterations in vascular conductance with only minimal contributions from Q to the initial reflex MAP response. Thus, the capacity of the CBR to regulate blood pressure depends critically on its ability to alter vascular tone both at rest and during exercise. This review will emphasize the utility of the variable pressure neck chamber to assess CBR function in human experimental investigations and the mechanisms by which the CBR responds to alterations in arterial blood pressure both at rest and during exercise. [source] Control of human articular chondrocyte differentiation by reduced oxygen tensionJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2004Christopher L. Murphy Cell number is often a limiting factor in studies of chondrocyte physiology, particularly for human investigations. Chondrocytes can be readily proliferated in monolayer culture, however, differentiated phenotype is soon lost. We therefore endeavored to restore normal phenotype to human chondrocytes after serial passage in monolayer culture by manipulating cell morphology and oxygen tension towards the in vivo state. Third passage cells were encapsulated in alginate and exposed to either 20% or more physiologic 5% oxygen tensions. To assess cell phenotype, gene expression was measured using TaqMan real-time PCR. Encapsulated, primary chondrocytes cultured in 20% oxygen were used as a positive reference. Passaged human chondrocytes were fibroblastic in appearance and had lost normal phenotype as evidenced by a decrease in expression of collagen II, aggrecan, and sox9 genes of 66, 6, and 14 fold, respectively; with concomitant high expression of type I collagen (22 fold increase). A partial regaining of the differentiated phenotype was observed by encapsulation in 20% oxygen; however, even after 4 weeks, collagen II gene expression was not fully restored. Collagen II and aggrecan expression were increased, on average, 3 fold, in 5% oxygen tension compared to 20% cultures. Furthermore, matrix glycosaminoglycan (GAG) levels were significantly increased in reduced oxygen. In fact, after 4 weeks in 5% oxygen, encapsulated third passage cells had collagen II expression fully regained and aggrecan and sox9 levels actually exceeding primary cell levels in 20% oxygen. Our results show that the phenotype of serially passaged human articular chondrocytes is more fully restored by combining encapsulation with culture in more physiological levels of oxygen. Sox9, an essential transcription factor for chondrocyte differentiation is strongly implicated in this process since its expression was upregulated almost 27 fold. These findings have implications for the optimal conditions for the in vitro culture of chondrocytes. © 2004 Wiley-Liss, Inc. [source] Angiogenesis Therapy for the Treatment of Erectile DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 7 2010Jeffrey J. Lysiak PhD ABSTRACT Introduction., Over the past 15 years, significant advances have been made in the treatment of erectile dysfunction (ED). The most significant of these advances has been pharmacological treatment of ED with phosphodiesterase type 5 (PDE5) inhibitors. This therapy greatly increased the awareness of ED and has helped stimulate research into the underlying causes of ED. While treatment with PDE5 inhibitors continues to be the current therapy of choice, approximately 40% of men treated with PDE5 inhibitors fail to have significant improvement in erectile function and PDE5 inhibitors do not reverse the vasculopathic processes associated with ED. With this in mind, new therapies must be developed. The treatment with angiogenic growth factors such as vascular endothelial cell growth factor (VEGF) may be one such therapy. Aim., This review will focus on defining key terms in the angiogenic process, angiogenic growth factors, and different delivery methods, and summarize results from angiogenic therapies for the treatment of ED. Methods., A review of the literature was performed on all angiogenic therapies for the treatment of ED. A brief review on the angiogenic factors was also performed Results., Angiogenic therapies for the treatment of ED are possible and promising; however, further investigation is needed to advance clinically. Conclusions., Although numerous studies have now employed angiogenic factors for the possible treatment of ED in several animal models, we are still not at the point to begin human investigations. Future studies need to examine proper dosage of the angiogenic agent, route of delivery, time course for delivery, and combination therapies. Lysiak JJ, Kavoussi PK, Ellati RT, Steers WD, and Annex BH. Angiogenesis therapy for the treatment of erectile dysfunction. J Sex Med 2010;7:2554,2563. [source] | |||||||||||||