Among the subsets that define hematopoietic stem cells (HSCs), CD34- c-kit+ Sca-1+ lineage marker- (CD34-KSL) cells are regarded as one of the populations that have the highest enrichment of HSCs in adult mouse bone marrow. Here, we demonstrate that long-term repopulating hematopoietic stem cells (LTR-HSCs) have high expression of CD61 (integrin beta3) within the CD34-KSL population. Approximately 60% of CD34-KSL cells showed high expression of CD61. CD61HighCD34-KSL populations also exhibited significantly greater properties of HSC, such as expression of HSC markers, the side population (SP) phenotype, and ability for long-term repopulation. In both SP cells and non-SP (NSP) cells, CD61HighCD34-KSL cells also contained significantly more LTR-HSCs than CD61Low/-CD34-KSL cells. Our results indicate that CD61 is exploitable for HSC enrichment as a supportive positive cell surface marker.

Breast cancer is the leading cause of cancer death for women worldwide. While breast cancer incidence is lower for many ethnic minority women than for white women, stage at diagnosis and survival are often worse. These disparities are most marked for African-American women, but are also present for Asians, Latinas, Native Americans and Hawaiians. The etiology of ethnic disparities in breast cancer is multifactorial, including differences in tumor characteristics, genetics, access to care and insurance, prevalence of risk factors, screening participation and processes of care, such as timeliness of diagnosis and quality of communication and treatment. This review will examine what is known regarding ethnic differences in all of these areas, what questions remain, and where researchers and policy makers should focus their future efforts.

Many argue that high costs of pharmaceutical research and development leads to high drug-prices and that existing prices are necessary to fund future expenditures on research and development. However, high pharmaceutical-prices can limit patient access to life-saving therapeutics. This paper examines the impact of high prices on patients and the relation between prices and innovation, and finally, considers policies that may balance patients' access to medications and financial rewards to industry.

Communicating bad news to patients and their families is a difficult but routine responsibility for hospitalists. Most practitioners have little or no formal training for this task. Preparation for, delivery of, and follow-up to these conversations should be deliberately planned in order to meet patients' needs. In this article, we review the literature that guides this process and, with a case example, describe steps practitioners can take to effectively deliver bad news and pitfalls that should be avoided. As competency in this skill set is necessary for effective patient care, hands-on training should be part of the core curriculum for all health care practitioners. Hospitalists should be proficient in this area and may serve as role models and instructors for colleagues and trainees.

Human mast cell tryptases vary strikingly in secretion, catalytic competence, and inheritance. To explore the basis of variation, we compared genes from a range of primates, including humans, great apes (chimpanzee, gorilla, orangutan), Old- and New-World monkeys (macaque and marmoset), and a prosimian (galago), tracking key changes. Our analysis reveals that extant soluble tryptase-like proteins, including alpha- and beta-like tryptases, mastins, and implantation serine proteases, likely evolved from membrane-anchored ancestors because their more deeply rooted relatives (gamma tryptases, pancreasins, prostasins) are type I transmembrane peptidases. Function-altering mutations appeared at widely separated times during primate speciation, with tryptases evolving by duplication, gene conversion, and point mutation. The alpha-tryptase Gly(216)Asp catalytic domain mutation, which diminishes activity, is present in macaque tryptases, and thus arose before great apes and Old World monkeys shared an ancestor, and before the alphabeta split. However, the Arg(-3)Gln processing mutation appeared recently, affecting only human alpha. By comparison, the transmembrane gamma-tryptase gene, which anchors the telomeric end of the multigene tryptase locus, changed little during primate evolution. Related transmembrane peptidase genes were found in reptiles, amphibians, and fish. We identified soluble tryptase-like genes in the full spectrum of mammals, including marsupial (opossum) and monotreme (platypus), but not in nonmammalian vertebrates. Overall, our analysis suggests that soluble tryptases evolved rapidly from membrane-anchored, two-chain peptidases in ancestral vertebrates into soluble, single-chain, self-compartmentalizing, inhibitor-resistant oligomers expressed primarily by mast cells, and that much of present numerical, behavioral, and genetic diversity of alpha- and beta-like tryptases was acquired during primate evolution.