Health Services in China

In the face of the adverse condition of overpopulation, limited resources and technological backwardness shared by the developing nations, at least one country, the People's Republic of China, is attempting to devise a health system which rejects Western standards of medical care and its inherent biases and is geared rather to meet the needs of the local population. This system relies on extensive and often intensive use of traditional practitioners, health teams and medical auxiliaries in an attempt to make health and medical care available to most of China's 80% rural population. By focusing on training and deployment of medical and health personnel, the Chinese are seeking to avoid the burden of large investments in curative medicine accessible only to wealthy urban elites which plagues many other developing countries

The pituitary TGFb1 system as a novel target for the treatment of resistant prolactinomas

Prolactinomas are the most frequently observed pituitary adenomas and most of themrespond well to conventional treatment with dopamine agonists (DAs). However, a subsetof prolactinomas fails to respond to such therapies and is considered as DA-resistantprolactinomas (DARPs). New therapeutic approaches are necessary for these tumors.Transforming growth factor b1 (TGFb1) is a known inhibitor of lactotroph cell proliferationand prolactin secretion, and it partly mediates dopamine inhibitory action. TGFb1 is secretedto the extracellular matrix as an inactive latent complex, and its bioavailability is tightlyregulated by different components of the TGFb1 system including latent binding proteins,local activators (thrombospondin-1, matrix metalloproteases, integrins, among others), andTGFb receptors. Pituitary TGFb1 activity and the expression of different components of theTGFb1 system are regulated by dopamine and estradiol. Prolactinomas (animal models andhumans) present reduced TGFb1 activity as well as reduced expression of several componentsof the TGFb1 system. Therefore, restoration of TGFb1 inhibitory activity represents a noveltherapeutic approach to bypass dopamine action in DARPs. The aim of this review is tosummarize the large literature supporting TGFb1 important role as a local modulator ofpituitary lactotroph function and to provide recent evidence of the restoration of TGFb1activity as an effective treatment in experimental prolactinomasFil: Recouvreux, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Cedars Sinai Medical Center; Estados UnidosFil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rifkin, Daniel B.. University of New York; Estados UnidosFil: Diaz, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Plasminogen Activator in Differentiating Mouse Keratinocytes

The activity of the serine protease plasminogen activator (PA) was measured in cell lysates from primary mouse keratinocyte cultures as well as from a number of established mouse keratinocyte lines. Enzyme activity was generally higher in the transformed lines than in the primary cultures; however, among the lines tested, those that expressed the highest degree of morphologic differentiation had the highest levels of cell-associated PA. In both the normal (primary) and transformed (established) keratinocyte cultures, PA activity increased when cultures reached confluence and morphologic evidence of differentiation was noted. The highest specific activity of the enzyme was found in cells shed from differentiating cultures, which consisted predominantly of detergent-resistant cornified envelopes. As the cultures differentiated and these cells were shed from the culture surface, the total cell-associated PA activity of the culture decreased accordingly. In both the normal and transformed keratinocyte cultures, peak PA activity occurred at a time when DNA synthesis was declining. These findings indicate that as keratinocytes differentiate, their intracellular levels of PA increase. The modulation of this endogenous keratinocyte enzyme may play an important, although as yet undefined, role in the normal maturation and terminal differentiation of these cells

Latent TGF-β binding protein-3 (LTBP-3) requires binding to TGF-β for secretion

AbstractLatent transforming growth factor-β (TGF-β) binding protein (LTBP)-1, which is easily secreted, has been shown to enhance the secretion of TGF-β. Here we show that another member of the LTBP family, LTBP-3, is not secreted by several cell types, but secretion occurs after coexpression with TGF-β. The secretion of LTBP-3 requires complexing of LTBP-3 with Cys33 of the TGF-β propeptide

A Unifying View of Multiple Kernel Learning

Recent research on multiple kernel learning has lead to a number of approaches for combining kernels in regularized risk minimization. The proposed approaches include different formulations of objectives and varying regularization strategies. In this paper we present a unifying general optimization criterion for multiple kernel learning and show how existing formulations are subsumed as special cases. We also derive the criterion's dual representation, which is suitable for general smooth optimization algorithms. Finally, we evaluate multiple kernel learning in this framework analytically using a Rademacher complexity bound on the generalization error and empirically in a set of experiments

Integrin αVβ6-mediated activation of latent TGF-β requires the latent TGF-β binding protein-1

Transforming growth factor-βs (TGF-β) are secreted as inactive complexes containing the TGF-β, the TGF-β propeptide, also called the latency-associated protein (LAP), and the latent TGF-β binding protein (LTBP). Extracellular activation of this complex is a critical but incompletely understood step in TGF-β regulation. We have investigated the role of LTBP in modulating TGF-β generation by the integrin αVβ6. We show that even though αvβ6 recognizes an RGD on LAP, LTBP-1 is required for αVβ6-mediated latent TGF-β activation. The domains of LTBP-1 necessary for activation include the TGF-β propeptide-binding domain and a basic amino acid sequence (hinge domain) with ECM targeting properties. Our results demonstrate an LTBP-1 isoform-specific function in αVβ6-mediated latent TGF-β activation; LTBP-3 is unable to substitute for LTBP-1 in this assay. The results reveal a functional role for LTBP-1 in latent TGF-β activation and suggest that activation of specific latent complexes is regulated by distinct mechanisms that may be determined by the LTBP isoform and its potential interaction with the matrix