Health Care Efficiencies: Consolidation and Alternative Models vs. Health Care and Antitrust Regulation - Irreconcilable Differences?

Despite the U.S. substantially outspending peer high income nations with almost 18% of GDP dedicated to health care, on any number of statistical measurements from life expectancy to birth rates to chronic disease, the U.

Inflammation and immunity in organ regeneration.

The ability of vertebrates to regenerate amputated appendages is increasingly well-understood at the cellular level. Cells mediating an innate immune response and inflammation in the injured tissues are a prominent feature of the limb prior to formation of a regeneration blastema, with macrophage activity necessary for blastema growth and successful development of the new limb. Studies involving either anti-inflammatory or pro-inflammatory agents suggest that the local inflammation produced by injury and its timely resolution are both important for regeneration, with blastema patterning inhibited in the presence of unresolved inflammation.

Neuropeptides as biologial system integrators – mini review.

This paper provides a review on the emerging role of neuropeptides for body systems integration. Neuropeptides are small protein-like substances that are released into the synaptic space and/or the blood, hence, acting as neurotransmitters and neurohormones. Classically, their role has been viewed as integrating the central nervous system and the endocrine system.

Changes in the inflammatory response to injury and its resolution during the loss of regenerative capacity in developing Xenopus limbs.

Tissue and organ regeneration, unlike development, involves an injury that in postembryonic animals triggers inflammation followed by resolution. How inflammation affects epimorphic regeneration is largely uninvestigated. Here we examine inflammation and its resolution in Xenopus laevis hindlimb regeneration, which declines during larval development.

The developing Xenopus limb as a model for studies on the balance between inflammation and regeneration.

The roles of inflammation and immune cell reactivity triggered by amputation have only recently begun to be addressed in investigations of epimorphic regeneration, although studies of tissue repair in mammals clearly show the importance of the immune system in determining the quality of the repair process. Here, we first review inflammation-related work in non-mammalian systems of epimorphic regeneration which suggests that regeneration of an amputated appendage requires continuous modulation of the local immune response, from the first hours after amputation through the period of blastema patterning. We then present data on the effects of anti-inflammatory and proinflammatory agents on regeneration of larval Xenopus hindlimbs.

Dedifferentiation and the role of sall4 in reprogramming and patterning during amphibian limb regeneration.

A central feature of epimorphic regeneration during amphibian limb regeneration is cellular dedifferentiation. Two questions are discussed. First, what is the origin and nature of the soluble factors involved in triggering local cellular and tissue dedifferentiation? Secondly, what role does the key stem cell transcription factor Sall4 play in reprogramming gene expression during dedifferentiation? The pattern of Sall4 expression during Xenopus hindlimb regeneration is consistent with the hypothesis that Sall4 plays a role in dedifferentiation (reprogramming) and in maintaining limb blastema cells in an undifferentiated state.

Proteomic analysis of blastema formation in regenerating axolotl limbs.

Background: Following amputation, urodele salamander limbs reprogram somatic cells to form a blastema that self-organizes into the missing limb parts to restore the structure and function of the limb. To help understand the molecular basis of blastema formation, we used quantitative label-free liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)-based methods to analyze changes in the proteome that occurred 1, 4 and 7 days post amputation (dpa) through the mid-tibia/fibula of axolotl hind limbs.

Results: We identified 309 unique proteins with significant fold change relative to controls (0 dpa), representing 10 biological process categories: (1) signaling, (2) Ca2+ binding and translocation, (3) transcription, (4) translation, (5) cytoskeleton, (6) extracellular matrix (ECM), (7) metabolism, (8) cell protection, (9) degradation, and (10) cell cycle.

RNA helicase Ddx39 is expressed in the developing central nervous system, limb, otic vesicle, branchial arches and facial mesenchyme of Xenopus laevis.

Ddx39, a DEAD-box RNA helicase, is a part of the homeostatic machinery that regulates the switch between cellular proliferation and differentiation. Ddx39 was shown to be differentially regulated in Xenopus laevis using a differential screen of mRNAs from regenerating limbs (King et al., 2003).

Gene expression profiles of lens regeneration and development in Xenopus laevis.

Seven hundred and thirty-four unique genes were recovered from a cDNA library enriched for genes up-regulated during the process of lens regeneration in the frog Xenopus laevis. The sequences represent transcription factors, proteins involved in RNA synthesis/processing, components of prominent cell signaling pathways, genes involved in protein processing, transport, and degradation (e.g.

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration.

During amphibian epimorphic limb regeneration, local injury produces metabolic changes that lead to cellular dedifferentiation and formation of a blastema, but few details of these changes have been elucidated. Here we report the first global proteomic analysis of epimorphic regeneration comparing the profiles of abundant proteins in larval limbs of the anuran Xenopus laevis (stage 53) at the time of amputation (0dPA) and 3 days post-amputation when the regeneration blastema is developing (3dPA). We identified and quantified 1517 peptides, of which 1067 were identified with high peptide ID confidence.

Loss of the protein NUPR1 (p8) leads to delayed LHB expression, delayed ovarian maturation, and testicular development of a sertoli-cell-only syndrome-like phenotype in mice.

The high mobility group factor NUPR1, also known as p8 and com1, plays a role in temporal expression of the beta subunit of luteinizing hormone, LHB, during gonadotroph development. At Embryonic Day (e) 16.5, LHB is detectable in wild-type (Nupr1(+/+)) but not Nupr1 knockout (Nupr1(-/-)) mice.

Neural MMP-28 expression precedes myelination during development and peripheral nerve repair.

Mammalian matrix metalloproteinase 28 (MMP-28) is expressed in several normal adult tissues, and during cutaneous wound healing. We show that, in frog and mouse embryos, MMP-28 is expressed predominantly throughout the nervous system. Xenopus expression increases during neurulation and remains elevated through early limb development where it is expressed in nerves.

DP58, an inducible myeloid protein, is constitutively expressed in murine neuronal nuclei.

A novel cytosolic phosphoprotein, DP58 induced in bone marrow-derived dendritic progenitors was found in this study to be constitutively expressed at a very high level in neuronal nuclei. Amplified cDNA confirmed by sequencing to be DP58 was present only in brain tissue, and DP58-like protein was expressed in neurons as a 52 kDa nuclear protein, phosphorylated primarily at the serine residues. In contrast, its isoform in dendritic progenitors appeared as a 58 kDa inducible protein with phosphorylation at serine, threonine and tyrosine residues.

Global analysis of gene expression in Xenopus hindlimbs during stage-dependent complete and incomplete regeneration.

Xenopus laevis tadpoles are capable of limb regeneration after amputation, in a process that initially involves the formation of a blastema. However, Xenopus has full regenerative capacity only through premetamorphic stages. We have used the Affymetrix Xenopus laevis Genome Genechip microarray to perform a large-scale screen of gene expression in the regeneration-complete, stage 53 (st53), and regeneration-incomplete, stage 57 (st57), hindlimbs at 1 and 5 days postamputation.

Expression of Xenopus XlSALL4 during limb development and regeneration.

The multi-C2H2 zinc-finger domain containing transcriptional regulators of the spalt (SAL) family plays important developmental regulatory roles. In a competitive subtractive hybridization screen of genes expressed in Xenopus laevis hindlimb regeneration blastemas, we identified a SAL family member that, by phylogenetic analysis, falls in the same clade as human SALL4 and have designated it as XlSALL4. Mutations of human SALL4 have been linked to Okihiro syndrome, which includes preaxial (anterior) limb defects.

Identification of genes expressed during Xenopus laevis limb regeneration by using subtractive hybridization.

Suppression polymerase chain reaction-based subtractive hybridization was used to identify genes that are expressed during Xenopus laevis hindlimb regeneration. Subtractions were done by using RNAs extracted from the regeneration-competent stage (stage 53) and regeneration-incompetent stage (stage 59) of limb development. Forward and reverse subtractions were done between stage 53 7-day blastema and stage 53 contralateral limb (competent stage), stage 59 7-day pseudoblastema and stage 59 contralateral limb (incompetent stage), and stage 53 7-day blastema and stage 59 7-day pseudoblastema.

Regeneration or scarring: an immunologic perspective.

Complete regeneration of complex tissues and organs is usually precluded by fibrotic reactions that lead to scarring. Fish, salamanders, and larval anurans are among the few vertebrates capable of regenerating lost appendages, and this process seems to recapitulate ontogenic development of the structure in most respects. Recent work has revealed a capacity for excellent regeneration in certain mammalian tissues: embryonic or fetal skin and the ear of the MRL mouse.