Osteopontin (OPN) is a phosphorylated acidic glycoprotein that has been implicated in a number of physiological and pathological events, including maintenance or reconfiguration of tissue integrity during inflammatory processes. As such, it is required for stress-induced bone remodeling and certain types of cell-mediated immunity. It also acts in dystrophic calcification, coronary restenosis, and tumor cell metastasis. An RGD-containing protein, OPN exists both as an immobilized ECM molecule in mineralized tissues and as a cytokine in body fluids; it is not a significant part of typical nonmineralized ECM.OPN can engage a number of receptors, including the integrins α v (β 1 , β 3 , or β 5 ) and (α 4 , α 5 , α 8 , or α 9 )β 1 , and it may also be a ligand for certain variant forms of CD44, specifically v6 and/or v7, but possibly only in conjunction with a β 1 integrin (1). These receptors directly or indirectly activate cellular signaling pathways, allowing OPN to mediate cell-matrix, and possibly cell-cell, interactions. Several studies have demonstrated that OPN delivers a prosurvival, antiapoptotic signal to the cell. Here, we argue that OPN influences cellular functions in a unique manner, by mimicking key aspects of an ECM signal outside the confines of the ECM. We will explore this idea by reviewing recent data concerning OPN signaling and the consequences of OPN deficiency in several settings, notably inflammatory processes involving immune cells and bone cells. Figure 1 illustrates some of the features of the OPN molecule. The presence of a conserved thrombin cleavage site suggests that certain physiological processes employing OPN depend upon its cleavage by thrombin. Some of these adhesive interactions involve the RGD sequence, which is found in various ECM proteins and binds directly to many integrins. Both RGD-dependent and RGD-independent OPN-receptor interactions are modulated by thrombin cleavage of OPN. For instance, thrombin-cleaved OPN, but not intact OPN, can support RGD-dependent migration of melanoma cells (2). Likewise, K562 erythroleukemia cells bind via activated α 5 β 1 to the RGD sequence in thrombin-cleaved OPN. A non-RGD-dependent interaction with α 9 β 1 offers yet another example: only after cleavage by thrombin can human OPN interact with α 9 β 1 via the sequence SVVYGLR, which is located between the RGD sequence and the thrombin cleavage site (3). This binding motif is also responsible for the RGD-independent binding of the J6 T-cell line to activated α 4 β 1 , but in the latter case, cleavage by thrombin is not required for binding of OPN by activated integrin (4). Adhesion of B lymphocytes via α v β 3 also occurs via a cryptic binding site masked in intact OPN, and TPA-activated B lymphocytes attach more effectively to thrombincleaved OPN than to full-length OPN (5). In contrast, Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival OPN-integrin interactions: consequences of cleavage by thrombin

Previous quantitative reviews of research on the efficacy of psychotherapy for depression have included only a subset of the available research or limited their focus to a single outcome measure. The present review offers a more comprehensive quantitative integration of this literature. Using studies that compared psychotherapy with either no treatment or another form of treatment, this article assesses (a) the overall effectiveness of psychotherapy for depressed clients, (b) its effectiveness relative to pharmacotherapy, and (c) the clinical significance of treatment outcomes. Findings from the review confirm that depressed clients benefit substantially from psychotherapy, and these gains appear comparable to those observed with pharmacotherapy. Initial analysis suggested some differences in the efficacy of various types of treatment; however, once the influence of investigator allegiance was removed, there remained no evidence for the relative superiority of any 1 approach. In view of these results, the focus of future research should be less on differentiating among psychotherapies for depression than on identifying the factors responsible for improvement. Depression is a prevalent clinical disorder with high economic and emotional costs. Epidemiological research has indicated that 10%-20% of the population experience a major depressive episode at some point in their lifetime (Boyd & Weissman, 1981), with the incidence highest during the adult years when family and career responsibilities may be most adversely affected (Weissman & Myers, 1978). Although the remission rate for depressive disorders is relatively high (Beck, 1967, chap. 3), a substantial portion of those afflicted remain chronically depressed (Weissman & Klerman, 1977), and those who do improve are at an increased risk for further episodes (Belsher & Costello, 1988;Kessler, 1978; Klerman, 1978). Until recently, depression was treated almost exclusively with medication, traditional insight-oriented therapy, or a combination of the two. However, the 1970s witnessed the development of a number of new therapeutic approaches, each of which pos

This review quantitatively assesses the outcomes of psychotherapy with children. Seventy-five studies were examined in which children who received psychotherapy were compared with controls or children receiving another form of treatment. Results demonstrated that therapy with children is similar in effectiveness to therapy with adults; treated children achieved outcomes about two thirds of a standard deviation better than untreated children. Although behavioral treatments appeared to be more effective than nonbehavioral treatments, this apparent superiority was due largely to the types of outcome and target problems included in behavioral studies. No differences in outcome were found to result from other treatment characteristics such as the use of play in therapy or the administration of treatment individually or in groups. The evidence from this review suggests that previous doubts about the overall efficacy of psychotherapy with children can be laid to rest.

Osteopontin (Opn) is a secreted adhesive, glycosylated phosphoprotein that contains the arginine-glycine-aspartic acid (RGD) cell-binding sequence that is found in many extracellular matrix (ECM) proteins (for a review of Opn see References Denhardt & Guo 1993; Patarca et al. 1993; Rittling & Denhardt 1999). Since its initial description in 1979 as a secreted protein associated with malignant transformation, Opn has been independently discovered by investigators from diverse scientific disciplines, and has been associated with a remarkable range of pathologic responses. Opn is an important bone matrix protein, where it is thought to mediate adhesion of osteoclasts to resorbing bone. However, studies from the past decade have identified an alternative role for Opn as a key cytokine regulating tissue repair and inflammation. Recent work by our laboratory and that of others has underlined the importance of Opn as a pivotal cytokine in the cellular immune response. Despite this Opn is not well known to the immunologist. In this review we will focus on studies that pertain to the role of Opn in cell-mediated and granulomatous inflammation.

We examined 17 meta‐analyses of comparisons of active treatments with each other, in contrast to the more usual comparisons of active treatments with controls. These meta‐analyses yielded a mean uncorrected absolute effect size for Cohen's d of .20, which is small and non‐significant (an equivalent Pearson's r would be. 10). The smallness of this effect size confirms Rosenzweig's supposition in 1936 about the likely results of such comparisons. In the present sample, when such differences were corrected for the therapeutic allegiance of the researchers involved in comparing the different psychotherapies, these differences tend to become even further reduced in size and significance, as shown previously by Luborsky, Diguer, Seligman, et al. (1999).