Personal care product use and urinary levels of phthalate metabolites in Mexican women.

Sources of phthalates other than Polyvinyl chloride (PVC) related products are scarcely documented in Mexico. The objective of our study was to explore the association between urinary levels of nine phthalate metabolites and the use of personal care products. Subjects included 108 women who participated as controls in an ongoing population-based case-control study of environmental factors and genetic susceptibility to breast cancer in northern Mexico.

Ethyl glucuronide, ethyl sulfate, and ethanol in urine after sustained exposure to an ethanol-based hand sanitizer.

To assess the degree of ethanol absorption and subsequent formation of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) following sustained application of hand sanitizer, 11 volunteers cleansed their hands with Purell(™) hand sanitizer (62% ethanol) every 5 min for 10 h on three consecutive days. Urine specimens were obtained at the beginning and end of each day of the study, and on the morning of the fourth day. Urinary creatinine, ethanol, EtG, and EtS concentrations were measured.

Comparing genetic ancestry and self-reported race/ethnicity in a multiethnic population in New York City.

Self-reported race/ethnicity is frequently used in epidemiological studies to assess an individual's background origin. However, in admixed populations such as Hispanic, self-reported race/ethnicity may not accurately represent them genetically because they are admixed with European, African and Native American ancestry. We estimated the proportions of genetic admixture in an ethnically diverse population of 396 mothers and 188 of their children with 35 ancestry informative markers (AIMs) using the STRUCTURE version 2.

Acellular dermal matrix for the treatment and prevention of implant-associated breast deformities.

Background: Acellular dermal matrix has been increasingly accepted in prosthetic breast reconstruction. Observed benefits include improved control and support of implant position, better implant coverage, and the suggestion of a decreased capsular contracture rate. Based on this positive experience, it is not surprising that acellular dermal matrix would be applied to other challenging implant-related problems.

Stem cells and osteoporosis therapy.

Skeletal remodeling requires recruitment of osteoblast precursors, in the form of MSCs, to the bone surface. In this issue of Cell Stem Cell, Wu et al. (2010) demonstrate that this event is mediated by osteoclastic mobilization of active transforming growth factor β1, which is inhibited by a common antiosteoporosis drug.

Calpain-6, a target molecule of glucocorticoids, regulates osteoclastic bone resorption via cytoskeletal organization and microtubule acetylation.

Glucocorticoids (GCs) inhibit the resorptive capacity of the osteoclast by disrupting its cytoskeleton. We find that calpain-6 (Capn6), a unique, nonproteolytic member of its family, is suppressed 12-fold by dexamethasone (DEX) in the bone-degrading cell. While Capn6 abundance parallels commitment of naive bone marrow macrophages (BMMs) to the osteoclast phenotype, its excess or deletion does not affect the cell's differentiation.

Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts.

Despite evidence that DAP12 regulates osteoclasts, mice lacking the ITAM-bearing protein exhibit only mild osteopetrosis. Alternatively, Dap12(-/-) mice, also lacking FcRgamma, are severely osteopetrotic, suggesting that FcRgamma compensates for DAP12 deficiency in the bone-resorbing polykaryons. Controversy exists, however, as to whether these co-stimulatory molecules regulate differentiation of osteoclasts or the capacity of the mature cell to degrade bone.

Fyn promotes proliferation, differentiation, survival and function of osteoclast lineage cells.

c-Src and Lyn are the only Src family kinases (SFKs) with established activity in osteoclasts (OCs). c-Src promotes function via cytoskeletal organization of the mature resorptive cell while Lyn is a negative regulator of osteoclastogenesis. We establish that Fyn, another SFK, also impacts the OC, but in a manner distinctly different than c-Src and Lyn.

High- and extra-high-projection breast implants: potential consequences for patients.

All breast implants can potentially have deleterious effects on patients' tissues. Limiting negative tissue consequences and potential uncorrectable deformities requires that surgeons be aware and educate patients regarding potential consequences of various implant designs. High-profile implants have been available for decades, and during the current decade, extra-high-profile implants have become available, but no valid peer-reviewed and published studies have compared the potential tissue consequences of these designs to those of other breast implant designs.

Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls.

Objectives: The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years.

Methods: The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California.

Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption.

Bone resorption requires the adhesion of osteoclasts to extracellular matrix (ECM) components, a process mediated by the alpha(v)beta(3) integrin. Following engagement with the ECM, integrin receptors signal via multiple downstream effectors, including the integrin-linked kinase (ILK). In order to characterize the physiological role of ILK in bone resorption, we generated mice with an osteoclast-specific Ilk gene ablation by mating mice with a floxed Ilk allele with TRAP-Cre transgenic mice.

Cdc42 regulates bone modeling and remodeling in mice by modulating RANKL/M-CSF signaling and osteoclast polarization.

The modeling and remodeling of bone requires activation and polarization of osteoclasts, achieved by reorganization of the cytoskeleton. Members of the Rho subfamily of small GTPases, including Cdc42, are known regulators of cytoskeletal components, but the role of these proteins in bone physiology and pathophysiology remains unclear. Here, we examined loss-of-function mice in which Cdc42 was selectively ablated in differentiated osteoclasts and gain-of-function animals wherein Cdc42Gap, a protein that inactivates the small GTPase, was deleted globally.

Microfibril-associated glycoprotein-1, an extracellular matrix regulator of bone remodeling.

MAGP1 is an extracellular matrix protein that, in vertebrates, is a ubiquitous component of fibrillin-rich microfibrils. We previously reported that aged MAGP1-deficient mice (MAGP1Delta) develop lesions that are the consequence of spontaneous bone fracture. We now present a more defined bone phenotype found in MAGP1Delta mice.

Integrins, growth factors, and the osteoclast cytoskeleton.

The unique ability of the osteoclast to degrade skeletal tissue depends upon formation of a resorptive microenvironment between the osteoclast and the bone surface. Generation of this privileged space is substantially mediated by signals emanating from alphavbeta3 integrin, which transits to its active high-affinity conformation by growth factor-initiated intracellular events targeting the matrix receptor's cytoplasmic domain. The activated liganded integrin stimulates a signaling complex consisting of c-Src, Syk, immunoreceptor tyrosine-based activation motif proteins, Slp-76, Vav3, and members of the Rho family of GTPases.

Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls.

Background: Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins.

Objectives: We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (2004-2007).

Methods: We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs).

Src-like adaptor protein regulates osteoclast generation and survival.

Src-like adaptor protein (SLAP) is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. We investigated the role of SLAP in osteoclast development and resorptive function.

Associations between polycyclic aromatic hydrocarbon-related exposures and p53 mutations in breast tumors.

Background: Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology.

Multiple genetic variants in telomere pathway genes and breast cancer risk.

Purpose: To explore the etiologic role of genetic variants in telomere pathway genes and breast cancer risk.

Methods: A population-based case-control study, the Long Island Breast Cancer Study Project, was conducted, and 1,067 cases and 1,110 controls were included in the present study. Fifty-two genetic variants of nine telomere-related genes were genotyped.

How do bone cells secrete proteins?

The ruffled border is the most specific marker of the active osteoclast (OC) as it forms only when the cell is resorbing bone. We provide evidence that this complex cytoskeletal structure reflects insertion of the lysosomal vesicles into the bone-apposed plasma membrane under the aegis of the Ca-sensing, exocytic protein, synaptotagmin VII (SytVII). In the manner, SytVII permits transport of matrix-degrading molecules into the resorptive microenvironment.

Dissection of platelet and myeloid cell defects by conditional targeting of the beta3-integrin subunit.

The purpose of this work was to determine platelet and myeloid cell-specific requirements for beta3-containing integrins in hemostasis, bone resorption, and tumor growth. LoxP-flanked mice were generated to study the conditional deletion of beta3-integrin in platelets [knockout in platelets (KOP)] and myeloid cells [knockout in myeloid (KOM)]. Using the beta3KOP and beta3KOM strains of mice, we studied the role of beta3-integrin in hemostasis, bone resorption, and subcutaneous tumor growth.

Gene promoter methylation is associated with increased mortality among women with breast cancer.

To better understand breast cancer etiology and progression, we explored the association between promoter methylation status of three breast cancer-related genes (BRCA1, APC, and p16) and survival in a large cohort of women with breast cancer. About 800 archived tumor tissues were collected from women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997. The vital status of the participants was followed through the end of year 2005 with a mean follow-up time of 8.

Defects in osteoblast function but no changes in long-term repopulating potential of hematopoietic stem cells in a mouse chronic inflammatory arthritis model.

Recent studies support the notion that there is an intricate relationship between hematopoiesis and bone homeostasis in normal steady states. Using mice undergoing chronic inflammatory arthritis, we investigated the relationship between hematopoiesis and bone homeostasis in pathologic conditions. We demonstrate that mice undergoing chronic inflammatory arthritis displayed osteoporosis resulting from a severe defect in osteoblast function.

Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival.

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR).