Cell Kinetic Basis for Pathophysiology of Psoriasis

Studies on the cell proliferation kinetics of psoriatic epidermal cells are presented and the results compared to similar studies for normal epidermis. The short 36-h duration of the psoriatic cell cycle (Tc) is confirmed with the first double-peaked fraction of labeled mitoses (FLM) curve in human subjects. The growth fraction of psoriasis using two experimental techniques approximates 100% within 36 h, confirming the rapid Tc found by the FLM method. The cell kinetic basis for the pathophysiology of psoriasis consists of at least 3 proliferative abnormalities in comparison to normal epidermis. By far the largest alteration is the shortening of the Tc from 311 to 36 h. There is also a doubling of the proliferative cell population in psoriasis from 27,000 to 52,000 cells/mm and an increase in the growth fraction from 60% to 100%. As a consequence of these abnormalities the psoriatic epidermis produces 35,000 cells/day from a proliferative compartment of 52,000 cells/mm2 surface area. This is a 28-fold greater production of cells than the 1,246 cells/day produced in normal epidermis. The biochemical or control factors leading to these kinetic differences continue to remain elusive

Topical Tritiated Thymidine for Epidermal Growth Fraction Determination

Direct autoradiographic identification of the epidermal growth fraction (GF) requires the delivery of tritiated thymidine ([3H]dThd) to the skin during the time interval of an entire cell cycle. The GF in normal human epidermis has not been directly measured using this technique because the systemic infusion of radioactive [3H]dThd in benign skin conditions is precluded by ethical considerations. Studies were undertaken to assess the feasibility of measuring the epidermal GF in vivo by the topical delivery of [3H]dThd. The percutaneous penetration of [3dThd in various vehicles was evaluated to select an effective topical delivery system. A vehicle consisting of Azone, isopropanol, and water (2:49:49) was the best of 4 different vehicles tested. The optimal penetration of [3H]dThd, with respect to the concentration of Azone over a range of 0–4%, was achieved at 2%. During the initial 24h following a single topical application of [3H]dThd to hairless mice the labeling increased linearly with time. In vivo studies in hairless mice produced a GF of 95% by both continuous systemic [3H]dThd infusion, and by twice daily topical [3H]dThd. Azone vehicles induced epidermal hyperplasia which was minimized by lowering the Azone concentration and by decreasing the frequency of applications from 24 to 48h. These studies establish the rationale for using topical delivery of [3H]dThd for the in vivo measurement of epidermal GF

Cell Kinetic Basis for Pathophysiology of Psoriasis

Studies on the cell proliferation kinetics of psoriatic epidermal cells are presented and the results compared to similar studies for normal epidermis. The short 36-h duration of the psoriatic cell cycle (Tc) is confirmed with the first double-peaked fraction of labeled mitoses (FLM) curve in human subjects. The growth fraction of psoriasis using two experimental techniques approximates 100% within 36 h, confirming the rapid Tc found by the FLM method. The cell kinetic basis for the pathophysiology of psoriasis consists of at least 3 proliferative abnormalities in comparison to normal epidermis. By far the largest alteration is the shortening of the Tc from 311 to 36 h. There is also a doubling of the proliferative cell population in psoriasis from 27,000 to 52,000 cells/mm and an increase in the growth fraction from 60% to 100%. As a consequence of these abnormalities the psoriatic epidermis produces 35,000 cells/day from a proliferative compartment of 52,000 cells/mm2 surface area. This is a 28-fold greater production of cells than the 1,246 cells/day produced in normal epidermis. The biochemical or control factors leading to these kinetic differences continue to remain elusive

Percutaneous Absorption of Methotrexate: Effect on Epidermal DNA Synthesis in Hairless Mice

One of the presumed reasons for the lack of clinical activity of topical methotrexate in psoriasis is insufficient percutaneous penetration necessary to inhibit epidermal DNA synthesis. The present study was undertaken to select a vehicle to optimize penetration of methotrexate in vitro and to determine the effects of this topical formulation on epidermal DNA synthesis in vivo in hairless mouse skin.Increased penetration of methotrexate was obtained in human skin in vitro with Vehicle N compared to water and n-decylmethylsulfoxide vehicles. Repeated topical application of this methotrexate/Vehicle N preparation produced marked epidermal atrophy in treated sites in both normal and hyperproliferative essential fatty acid deficient hairless mouse skin without similar effects at a distant skin site. Local inhibition of epidermal DNA synthesis was also obtained without systemic effects at a distant site. These studies demonstrate that methotrexate in Vehicle N may produce a direct effect on epidermis which may be useful for the topical therapy of psoriasis

How men view genetic testing for prostate cancer risk: findings from focus groups

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65567/1/j.1399-0004.2000.580303.x.pd

Unraveling the Helix Nebula: Its Structure and Knots

Through HST imaging of the inner part of the main-ring of the Helix Nebula together with CTIO 4-m images of the fainter outer parts, we have an unprecedented-quality view of the nearest bright planetary nebula. These images have allowed determination that the main-ring of the nebula is composed of an inner-disk of about 499\arcsec diameter (0.52 pc) surrounded by an outer-ring (in reality a torus) of 742\arcsec diameter (0.77 pc) whose plane is highly inclined to the plane of the disk. This outer-ring is surrounded by an outermost-ring of 1500\arcsec (1.76 pc) diameter which is flattened on the side colliding with the ambient interstellar medium. The inner-disk has an extended distribution of low density gas along its rotational axis of symmetry and the disk is optically thick to ionizing radiation, as is the outer-ring. Published radial velocities of the knots provides support for the two-component structure of the main-ring of the nebula and to the idea that the knots found there are expanding along with the nebular material from which it recently originated. There is a change in the morphology of the knots as a function of the distance from the local ionization front. This supports a scenario in which the knots are formed in or near the ionization front and are then sculpted by the stellar radiation from the central star as the ionization front advances beyond them.Comment: 30 pages, 20 figures, many figures have reduce fidelity for astroph preprint. Note: URLs in preprint were change

Double-crested Cormorants

The history of conflict between double-crested cormorants (Figure 1) and human interest in fisheries is long and convoluted. Following a low point in the 1970s, populations of cormorants expanded in North America, as did concerns about impacts on fisheries. By the late 1990s, natural resource agencies in 27 states reported losses of free-ranging fish stocks to cormorants. Agencies in 10 states, ranging from the Southwest to the Northeast, considered cormorant predation to be of moderate to major concern to fishery management. Overall, double-crested cormorants are not major consumers of commercial and sportfish species. However, exceptions have been recorded at specific sites with documented impacts on local fisheries (see Damage to Fisheries section). Cormorants often congregate and can have significant local impacts where high concentrations of fish occur, such as stocking release sites, private fishing ponds, aquaculture ponds, reservoirs, spawning sites, and other areas. Cormorants may be managed whenever their damage justi-fies the granting of the permits necessary to control them. Adult cormorants eat approximately 19 ounces of food per day, so local impacts of large flocks on fisheries can be substantial. Although cormorants frequently are blamed for reductions in fish harvests, this is not always substantiat-ed. Sometimes other factors, such as pollution, invasive species, and habitat loss may be the primary factor or con-tributing factors in the decline of fisheries

Regulation of artisanal small scale gold mining (ASGM) in Ghana and Indonesia as currently implemented fails to adequately protect aquatic ecosystems

Artisanal small scale gold mining (ASGM) operations are largely unregulated, informal and transient. Rudimentary mining and processing techniques used in ASGM often result in degraded environmental, safety, health and social conditions. ASGM requires permanent sources of water, placing most operations close to natural water bodies. Until recently, the impact on these environments has been largely overlooked, with most studies focussing primarily on mercury contamination and health concerns. Based on Ghanaian and Indonesian experiences, regulation of ASGM is a good step toward improvement, but here we argue that regulation alone is insufficient to improve environmental performance, particularly when the impacts of ASGM on aquatic ecosystems are largely unknown

Population genetic variation in gene expression is associated with phenotypic variation in Saccharomyces cerevisiae

BACKGROUND: The relationship between genetic variation in gene expression and phenotypic variation observable in nature is not well understood. Identifying how many phenotypes are associated with differences in gene expression and how many gene-expression differences are associated with a phenotype is important to understanding the molecular basis and evolution of complex traits. RESULTS: We compared levels of gene expression among nine natural isolates of Saccharomyces cerevisiae grown either in the presence or absence of copper sulfate. Of the nine strains, two show a reduced growth rate and two others are rust colored in the presence of copper sulfate. We identified 633 genes that show significant differences in expression among strains. Of these genes, 20 were correlated with resistance to copper sulfate and 24 were correlated with rust coloration. The function of these genes in combination with their expression pattern suggests the presence of both correlative and causative expression differences. But the majority of differentially expressed genes were not correlated with either phenotype and showed the same expression pattern both in the presence and absence of copper sulfate. To determine whether these expression differences may contribute to phenotypic variation under other environmental conditions, we examined one phenotype, freeze tolerance, predicted by the differential expression of the aquaporin gene AQY2. We found freeze tolerance is associated with the expression of AQY2. CONCLUSIONS: Gene expression differences provide substantial insight into the molecular basis of naturally occurring traits and can be used to predict environment dependent phenotypic variation

Defining forgiveness: Christian clergy and general population perspectives.

The lack of any consensual definition of forgiveness is a serious weakness in the research literature (McCullough, Pargament &amp; Thoresen, 2000). As forgiveness is at the core of Christianity, this study returns to the Christian source of the concept to explore the meaning of forgiveness for practicing Christian clergy. Comparisons are made with a general population sample and social science definitions of forgiveness to ensure that a shared meaning of forgiveness is articulated. Anglican and Roman Catholic clergy (N = 209) and a general population sample (N = 159) completed a postal questionnaire about forgiveness. There is agreement on the existence of individual differences in forgiveness. Clergy and the general population perceive reconciliation as necessary for forgiveness while there is no consensus within psychology. The clergy suggests that forgiveness is limitless and that repentance is unnecessary while the general population suggests that there are limits and that repentance is necessary. Psychological definitions do not conceptualize repentance as necessary for forgiveness and the question of limits has not been addressed although within therapy the implicit assumption is that forgiveness is limitless.</p