The secreted frizzled related protein 2 (SFRP2) gene is a target of the Pax2 transcription factor

Despite their essential role in vertebrate development, the function of Pax proteins in gene regulation is not well understood. To identify potential genes regulated by the Pax2 protein, we screened embryonic kidney cells transformed with Pax2-expressing retroviruses for genes activated in response to Pax2 expression. In this system, the gene encoding the secreted frizzled related protein, Sfrp2, was strongly activated in all Pax2b-expressing cells. This activation of Sfrp2 expression correlated with changes in chromatin structure at the Sfrp2 locus, particularly in and around regions of Pax2 binding. Although the amount of Pax2-dependent transactivation was low in transient assays, the data suggests that local alterations of chromatin structure by Pax proteins can greatly enhance expression when presented in the right cellular context.     

Ureteric bud outgrowth in response to RET activation is mediated by phosphatidylinositol 3-kinase

The c-ret gene encodes a receptor tyrosine kinase (RET) essential for the development of the kidney and enteric nervous system. Activation of RET requires the secreted neurotrophin GDNF (glial cell line-derived neurotrophic factor) and its high affinity receptor, a glycosyl phosphatidylinositol-linked cell surface protein GFRalpha1. In the developing kidney, RET, GDNF, and GFRalpha1 are all required for directed outgrowth and branching morphogenesis of the ureteric bud epithelium. Using MDCK renal epithelial cells as a model system, activation of RET induces cell migration, scattering, and formation of filopodia and lamellipodia. RET-expressing MDCK cells are able to migrate toward a localized source of GDNF. In this report, the intracellular signaling mechanisms regulating RET-dependent migration and chemotaxis are examined. Activation of RET resulted in increased levels of phosphatidylinositol 3-kinase (PI3K) activity and Akt/PKB phosphorylation. This increase in PI3K activity is essential for regulating the GDNF response, since the specific inhibitor, LY294002, blocks migration and chemotaxis of MDCK cells. Using an in vitro organ culture assay, inhibition of PI3K completely blocks the GDNF-dependent outgrowth of ectopic ureter buds. PI3K is also essential for branching morphogenesis once the ureteric bud has invaded the kidney mesenchyme. The data suggest that activation of RET in the ureteric bud epithelium signals through PI3K to control outgrowth and branching morphogenesis.     

Specific glycanforms of type IX collagen accumulate in embryonic chick sterna after 17 days of development

Type IX collagen is a key component of the extracellular matrix of cartilage where it occurs at the surfaces of type II collagen fibrils as a glycanated molecule. The function of the glycosaminoglycan (GAG) side chain of the molecule is, however, unknown. We have shown that type IX collagen in chicken sternal cartilage is synthesized with a unimodal distribution of GAG chain size, but at post 17 days of development three predominant glycanforms of type IX collagen accumulate. Such accumulation did not occur in sterna from day 15 embryos. In day 17 embryos predominant glycanforms were found in the caudal region of the sternum. By day 19 of development the three predominant glycanforms are widespread throughout the caudal and cephalic regions. The results indicate that developmental and anatomical changes occur to type IX collagen that depend on the size of the GAG chain attached to the alpha2(IX) chain of the molecule.      

Social status,social context,and arterial blood pressure

As social change and economic development have proceeded, the prevalence of chronic diseases, especially cardiovascular diseases, has increased in the developing world. In part this is due to the adoption of diets and other health behaviors characteristic of industrialized nations; in part it is a function of changing social and economic circumstances. In this paper, we describe the development and testing of a model designed to account for social and economic effects on cardiovascular disease risk. The model incorporates the fact that global economic processes have made a lifestyle characterized by the consumption of Euroamerican material goods and information a basis for the assignment of social status in local communities. But economic change at the local level is rarely sufficient to provide a foundation for individuals' status aspirations. Hence, many individuals attempt to maintain a lifestyle inconsistent with their economic standing, a variable we term lifestyle incongruity. Here we describe how this factor is associated with higher blood pressure in a variety of settings and also how the effects of lifestyle incongruity can be modified in local contexts by social class and social role processes. This latter process, contextual modification, is illustrated by data from American Samoa. In this example, the association of lifestyle incongruity with blood pressure is examined in 30 male household heads and 26 spouses. After an examination of Samoan ethnography focused attention on the importance of age and gender differences as defining social contexts of intracultural variation, the model was modified to assess interactions between age and gender as they affect the association of lifestyle incongruity and blood pressure. Lifestyle incongruity is strongly associated with higher systolic and diastolic blood pressure for the younger household heads, minimally associated with blood pressure for older household heads, and only slightly associated with the blood pressure of their spouses. The regression coefficients for the lifestyle incongruity by age by sex interaction term was significant at P ≤ 0.01 for both systolic and diastolic blood pressure. The consistency of these results with expectations based on the ethnographic record is emphasized in the interpretation. We feel that the lifestyle incongruity model represents an empirically successful attempt to link global political-economic processes, local social structure, and biological outcomes. Am J Phys Anthropol 102:55–66, 1997. © 1997 Wiley-Liss, Inc.     

Kidney development in cadherin-6 mutants: delayed mesenchyme-to-epithelial conversion and loss of nephrons

During nephrogenesis, dynamic changes in the expression of cell adhesion molecules are evident as epithelial structures differentiate from the induced mesenchyme. The cadherins are thought to play an important role in the metanephric mesenchyme, when cells aggregate to form the renal vesicle, a polarized epithelial structure which eventually fuses with the ureteric bud to generate a continuous nascent nephron. We have generated and analyzed mice with a targeted mutation in the gene encoding cadherin-6 (Cad-6), a type II cadherin expressed during early stages of nephrogenesis. These mice are viable and fertile, and they complete both early and late aspects of nephrogenesis. However, upon closer examination in vitro and in vivo, a fraction of the induced metanephric mesenchyme in Cad-6 mutant kidneys fails to form a fully polarized epithelium on schedule. Moreover, a significant number of the renal vesicles in Cad-6 mutant kidneys apparently fail to fuse to the ureteric bud. These alterations in epithelialization and fusion apparently lead to a loss of nephrons in the adult. These studies support the idea that cadherins play an essential role in the formation of epithelial structures and underscore the importance of timing in orchestrating the morphogenesis of complex epithelial tissues.     

Medical Anthropology: Toward a Third Moment in Social Science?

This article about medical anthropology was inspired by the work of Pierre Bourdieu, specifically, his efforts to reconcile the antinomy of a "social structuralist" and a "cultural constructivist" perspective. These perspectives are often opposed in the literature, but, in Bourdieu's view, human life cannot be studied without taking into account both how individuals are situated within and constrained by social structures and how those individuals construct an understanding of and impose meaning on the world around them. I argue that the special subject matter of medical anthropology--human health--demands that a synthetic approach be taken in our theory and research. I illustrate this argument with examples from my own research on social and cultural factors associated with blood pressure, and I point to other examples of this synthesis in medical anthropology. The results of this research hold promise for the continuing refinement of culture theory.     

Arterial Blood Pressure and Modernization in Brazil

The relationship between individual modernization and elevated arterial blood pressure was examined in a study in urban Brazil. We hypothesized that elevated blood pressure would result from the discrepancy between an individual's style of life and his or her economic resources; specifically, we suggested that when modern life-style acquisition exceeded economic resources, a circumstance referred to as "life-style stress," blood pressure would be elevated. This factor was related to diastolic, but not systolic, blood pressure, independently of a variety of biologic, dietary, and sociocultural confounding factors. The perceived change associated with life events also predicted diastolic, but not systolic, blood pressure. Other predictors of diastolic blood pressure were calcium intake, fat intake, race, age, and the body mass index. We argue that sociocultural risk factors emerge in the modernization process as a result of social structural imbalances generated by economic development and represent independent risk factors for elevated arterial blood pressure.