Biomedical subjects

Peter L Smith

Publications and source records attributed to Peter L Smith.

6 recordsLinked to original sources

PubMed2006

Kidney epithelial cells.

Kidney tubules are an essential component of an organism's blood clearance mechanism, recovering essential metabolites from glomerular filtration by active transport. Tubules are subject to injury, usually as the result of ischemia-reperfusion events that damage the polarized tubular cell layer that coats the tubule basement membrane, causing dysfunction and necrosis that is often associated with acute renal failure. However, tubules are capable of self-repair, forming new proximal tubular cells to replace failing or necrotic cells. The origin of the progenitor cells that give rise to new tubular cells is unknown. At one extreme, it is possible that all or a fraction of tubular cells can undergo a form of dedifferentiation and subsequent mitosis to form new tubular cells, or alternatively, it is possible that tubular regeneration follows the stem cell/transit-amplifying cell paradigm described for more rapidly regenerating organ systems. Regardless of the mechanism employed to generate new tubular cells, human tubular cells are readily grown in primary cultures and can recapitulate many of the metabolic, endocrine, and immunological properties attributable to endogenous renal proximal tubules when engrafted into bioartificial devices.

Adult Stem Cells↗

PubMed2005

Oscillator strength and linewidth measurements of dipole-allowed transitions in 14N2 between 93.5 and 99.5 nm.

Line oscillator strengths in 16 electric dipole-allowed bands of 14N2 in the 93.5-99.5 nm (106,950-100,500 cm(-1)) region have been measured at an instrumental resolution of 6.5 x 10(-4) nm (0.7 cm(-1)). The transitions terminate on vibrational levels of the 3psigma 1Sigma u (+), 3ppi 1Pi u, and 3ssigma 1Pi u Rydberg states and of the b' 1Sigma u (+) and b 1Pi u valence states. The J dependences of band f values derived from the experimental line f values are reported as polynomials in J'(J'+1) and are extrapolated to J'=0 in order to facilitate comparisons with results of coupled-Schrodinger-equation calculations that do not take into account rotational interactions. Most bands in this study reveal a marked J dependence of the f values and/or display anomalous P-, Q- and R-branch intensity patterns. These patterns should help inform future spectroscopic models that incorporate rotational effects, and these are critical for the construction of realistic atmospheric radiative transfer models. Linewidth measurements are reported for four bands. Information provided by the J dependences of the experimental linewidths should be of use in the development of a more complete understanding of the predissociation mechanisms in N2.

Journal Article↗

PubMed2005

Type I interferons and the innate immune response--more than just antiviral cytokines.

The role of type I interferon (referred to as IFN in this review) in early antiviral immunity is well known. More recently IFN has been shown to be a potent regulator of adaptive immunity. It is now becoming clear that a broad range of viruses, bacteria and even parasites express ligands capable of stimulating a growing number of signalling pathways that results in, often subtype specific, induction of IFN. Of particular interest are the signalling pathways associated with the Toll-like receptors. This family of receptors, each able to induce signals in response to a variety of ligands, initiates the pro-inflammatory response. They also contain members that have the capacity to induce IFN, making use of, and perhaps promoting the evolution of its pleiotropic responses. Greater knowledge of the events that result in induction of IFN is necessary in understanding the specificity of expression of an increasingly complex and important aspect of our immune system. This may reveal to us further therapeutic opportunities, either in the use of IFN or in the manipulation of their expression. This review details the established knowledge and recent advances made in understanding how and under what circumstances the IFNs are expressed, starting with brief overviews of IFN and Toll-like receptors before following the molecular processes from induction of IFN, activation of the JAK-STAT pathway and finally the expression of interferon stimulated genes and their functions.

Animals↗

PubMed2003

Doubly ionized carbon observed in the plasma tail of comet Kudo-Fujikawa.

Comet C/2002 X5 (Kudo-Fujikawa) was observed near its perihelion of 0.19 astronomical unit by the Ultraviolet Coronagraph Spectrometer aboard the Solar and Heliospheric Observatory spacecraft. Images of the comet reconstructed from high-resolution spectra reveal a quasi-spherical cloud of neutral hydrogen and a variable tail of C+ and C2+ that disconnects from the comet and subsequently regenerates. The high abundance of C2+ and C+, at least 24% relative to water, cannot be explained by photodissociation of carbon monoxide and is instead attributed to the evaporation and subsequent photoionization of atomic carbon from organic refractory compounds present in the cometary dust grains. This result serves to strengthen the connection between comets and the material from which the Solar System formed.

Carbon↗

PubMed2003

Strain-specific modification of lethality in fucose-deficient mice.

The FX locus encodes an essential enzyme in the de novo pathway of GDP-fucose biosynthesis. Mice homozygous for a targeted mutation of the FX gene manifest a host of pleiotropic abnormalities including a lethal phenotype that is almost completely penetrant in heterozygous intercrosses on a mixed genetic background. Here we have investigated genetic suppression of FX-mediated lethality. Reduced recovery of heterozygous mice was observed while backcrossing the null FX allele to C57BL/6J (B6), but was less dramatic in an outcross to CASA/Rk and absent in an outcross to 129S1/SvImJ, indicating that genetic background modifies survival of FX+/- progeny. Substantial strain-specific differences in pre- and postnatal survival of FX-/- progeny were also detected in heterozygous crosses of C57BL/6J congenic, 129S1B6F1, and B6CASAF1 mice. Specifically, intrauterine survival of FX-/- mice was greatly increased during a heterozygous intercross on a uniform C57BL/6J genetic background compared with survival on a hybrid genetic background consisting of a mixture of C57BL/6J and 129S2/SvPas. In addition, statistically significant clustering of FX-/- progeny into litters and specific breeding cages was noted during a B6CASAF1 FX+/- intercross, suggesting a rare mechanism for modifier gene action in which parentally expressed genes define the phenotype, in this case the survival potential, of mutant offspring. Our results disclose that lethality in FX mutant mice is determined by one or more strain-specific modifier loci.

Alleles↗

PubMed2002

Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus.

Glycoprotein fucosylation enables fringe-dependent modulation of signal transduction by Notch transmembrane receptors, contributes to selectin-dependent leukocyte trafficking, and is faulty in leukocyte adhesion deficiency (LAD) type II, also known as congenital disorder of glycosylation (CDG)-IIc, a rare human disorder characterized by psychomotor defects, developmental abnormalities, and leukocyte adhesion defects. We report here that mice with an induced null mutation in the FX locus, which encodes an enzyme in the de novo pathway for GDP-fucose synthesis, exhibit a virtually complete deficiency of cellular fucosylation, and variable frequency of intrauterine demise determined by parental FX genotype. Live-born FX(-/-) mice exhibit postnatal failure to thrive that is suppressed with a fucose-supplemented diet. FX(-/-) adults suffer from an extreme neutrophilia, myeloproliferation, and absence of leukocyte selectin ligand expression reminiscent of LAD-II/CDG-IIc. Contingent restoration of leukocyte and endothelial selectin ligand expression, general cellular fucosylation, and normal postnatal physiology is achieved by modulating dietary fucose to supply a salvage pathway for GDP-fucose synthesis. Conditional control of fucosylation in FX(-/-) mice identifies cellular fucosylation events as essential concomitants to fertility, early growth and development, and leukocyte adhesion.

Animals↗