bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Recombinant Interleukin-1α Is Proinflammatory in Normal Human Skin
Authors: Dowd Pauline M. , Camp Richard D.R. , Greaves Malcolm W.
Published: April 2009

The proinflammatory effects of recombinant human interleukin-1Α (HRIL-1Α) have been determined in the skin of normal human volunteers. Intradermal injection of 10, 50 and 100 U HRIL-1Α produced dose-related erythema which first appeared at 2 h, was maximal around 24 h, persisted for up to 48 h, and was associated with oedema. Histological examination revealed dermal mononuclear cell infiltrates, which were accompanied by neutrophils at 4 and 8 h. Injection of heat-treated HRIL-1Α (100 U) produced no erythema or oedema. These results demonstrate the potent proinflammatory properties of HRIL-1Α in human skin.
Involvement of Arachidonate-Dependent Lipid Mediators and Platelet-Activating Factor in Experimental Murine Contact Dermatitis
Authors: Csatò M. , Rosenbach T. , Czarnetzki B.M.
Published: April 2009

A 5-lipoxygenase inhibitor (5-LPI) and a platelet-activating factor antagonist (PAF-A) were studied in dinitrofluorobenzene (DNFB)-induced allergic and croton-oil-induced irritant murine contact dermatitis. Both inhibitors, at 1 and 5% concentrations, significantly reduced the ear swelling in allergic dermatitis while irritant dermatitis was far less affected. This suggests that 5-lipoxygenase-dependent mediators and PAF are involved in allergic contact dermatitis and that these mediators play only a minor role in irritant dermatitis.
Concentrations of Isotretinoin and the Arotinoid Ro 15-0778 in Plasma and Tissues of Hamsters and Rats
Authors: Vane Floie M. , Chari Sarita S. , Hurley James F. , Shapiro Stanley S.
Published: April 2009

The arotinoid Ro 15-0778 is a potent inhibitor of sebum secretion in rodents but not in humans, while isotretinoin (13-cis-retinoic acid, Accutane®) inhibits sebum secretion in rodents and humans. The concentrations of Ro 15-0778 and isotretinoin were determined in plasma and target tissues of castrated, testosterone-stimulated hamsters after oral and topical dosing and in castrated, testosterone-stimulated rats after oral dosing. Comparison of this concentration data to that obtained in the plasma and sebum of humans after dosing with Ro 15-00778 and with isotretinoin did not explain why Ro 15-0778 was a potent inhibitor of sebum production in rodents but not in humans.
Reconstructed Skin from Cultured Human Keratinocytes and Fibroblasts on a Collagen-Glycosaminoglycan Biopolymer Substrate
Authors: Boyce Steven , Michel Serge , Reichert Uwe , Shroot Braham , Schmidt Rainer
Published: April 2009

A lattice prepared from biopolymer substrate bovine skin collagen and chondroitin-6-sulfate (glycosaminoglycan) served as a support for normal human keratinocytes and fibroblasts. Air exposure of the lattice on an agarose block gave rise to reconstructed epidermis, the histological features of which are very similar to normal human epidermis. Indirect immunofluorescence staining of the plasma membrane-associated transglutaminase, the enzyme responsible for the synthesis of the cornified envelope, revealed the same tissue distribution as observed in vivo. Cell cycle analysis showed a large shift of the normal human keratinocyte population into S-phase and cell division during the 1st week postinoculation. Furthermore, the effects of two modulators of differentiation (25-hydroxycholesterol and sodium butyrate) on the reconstruction of the epidermis were evaluated.
Long-Term Cultured Adult Human Keratinocytes Secrete Granulocyte-Macrophage Colony-Stimulating Factor but Not Interleukin-3 after Cytokine Exposure in vitro
Authors: Owsianowski M. , Busch F.W. , Bonnekoh B. , Orfanos C.E.
Published: April 2009

To investigate the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and of interleukin-3 (IL-3) by human keratinocytes in vitro, adult human keratinocytes (aHKc) from 3 different donors and a spontaneously transformed keratinocytic line (HaCaT) were cultured and exposed to various cytokines and to the protein kinase C-activating agent phorbol-12-myristate-13-acetate (PMA). GM-CSF and IL-3 were measured by highly specific and sensitive immunoassays. Our findings showed that long-term cultured aHKc and HaCaT cells are capable of secreting GM-CSF but not IL-3 upon cytokine and PMA stimulation. Both interleukin-1 and tumor necrosis factor Α, which are known to be present in human epidermis, particularly during cutaneous inflammatory processes, were found to stimulate GM-CSF release. Therefore, we conclude that increased GM-CSF levels may play an important role in the interactions between epidermal keratinocytes and blood cells in vivo.
Effect of Ciclosporin on Epidermal 12(S)-Hydroxyeicosatetraenoic Acid Binding Sites
Authors: Arenberger Petr , Ruzicka Thomas , Kemény Lajos
Published: April 2009

12-Hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in the pathogenesis of inflammatory skin diseases. Recently, high-affinity binding sites for this eicosanoid have been identified on human keratinocytes by our group. Since ciclosporin exerts therapeutic effects in chronic inflammatory dermatoses such as psoriasis or atopic eczema, the influence of the drug on 12(S)-HETE binding to human keratinocytes was studied. No competitive inhibition of 12(S)-HETE binding was observed in ciclosporin concentrations between 10-10 and 10-6M. In contrast, pretreatment of epidermal cells for 24 h resulted in a dose-dependent decrease of specific 12(S)-HETE binding. The analysis of saturation curves showed that the inhibition of 12(S)-HETE binding by ciclosporin was due to the decrease of 12-HETE binding sites, while receptor affinity remained unchanged. In addition, ciclosporin blocked the interferon-γ-induced increase in epidermal 12(S)-HETE binding. These findings suggest that the effects of ciclosporin in cutaneous disorders could be partly mediated via an influence on epidermal 12(S)-HETE binding.
Antiviral Activity of 5-Iodo-2’-Deoxyuridine and Related Drugs in Human Keratinocytes Infected in vitro with Herpes simplex Virus Type 1
Authors: Reuveni H. , Bull C.O. , Landry M.L. , Milstone L.M. , Schwartz P.M.
Published: April 2009

5-Iodo-2′-deoxyuridine (IUDR) is a potent topical antiviral agent in experimental animals but is less active in man for treating cutaneous viral infections. We have shown here that IUDR is 5 times less active in human keratinocytes infected in vitro with herpes simplex virus type 1 than in guinea pig embryo cells infected in culture. To account, in part, for this difference in activity of IUDR, we measured the capacity of these different cultures to catabolize and thus inactivate the drug. IUDR is catabolized by thymidine phosphorylase; activity of this enzyme was very high in human keratinocytes in vitro but was very low in guinea pig embryo cells. The antiviral activity of IUDR in human keratinocytes, however, was not increased by inhibiting thymidine phosphorylase; inhibiting thymidine phosphorylase apparently increased the availability of thymidine that would compete with IUDR and, indeed, the activity of IUDR in infected cells was reduced by addition of thymidine to the medium. These data indicate that the catabolism of IUDR and related analogs alters antiviral activity in human keratinocytes.
Immunohistology of Human Allergic Late-Phase Skin Reactions
Authors: Frew A.J. , Varney V.A. , Gaga M. , Kay A.B.
Published: April 2009

Human late-phase allergic skin reactions (LPSR) are characterised histologically by a mixed infiltrate of granulocytes and mononuclear cells. Quantitative immunohistology reveals a correlation between the numbers of CD4+ T-cells and the number of activated eosinophils at LPSR sites. These CD4+ T-cells are predominantly CD45RO+ and belong to the ‘memory’ T-cell subset. Immunofluorescence studies indicate that type III (immune complex) mechanisms make no significant contribution to the LPSR. On the other hand, the LPSR and classical delayed-type hypersensitivity (DHT) both have a marked CD4+ T-cell component. T-cell infiltration is a more diffuse process in DTH than in the LPSR; between 24 and 48 h, DTH sites show a further increase in T-cell numbers with the appearance of CD8+ T-cells and an influx of monocytes. Activated eosinophils are present in the early stages of both LPSR and DTH, but are more prominent in the LPSR. These different patterns of cellular infiltration and activation are probably due to differences in the cytokine secretion pattern of the infiltrating T-cells. Detailed analysis of this hypothesis will require the use of in situ hybridization techniques.
Capsaicin: Actions on C Fibre Afferents That May Be Involved in Itch
Authors: Lynn Bruce
Published: April 2009

Capsaicin selectively excites C-polymodal nociceptors in mammalian skin. In the rat, the only species so far studied in detail, a long-term desensitization of a subpopulation of C-polymodal nociceptors occurs after the initial excitation. After nerve treatment, permanent loss of some C-polymodal nociceptors is found in the rat. It is argued that capsaicin must act primarily on C fibres involved in signalling about pain and not itch, although there may be overlap between the C afferents involved in these two nociceptive sensations. The possibility is raised that C mechanoreceptors, with their good histamine sensitivity, are also involved in itch.
Role of Transepidermal and Transfollicular Routes in Percutaneous Absorption of Hydrocortisone and Testosterone: In vivo Study in the Hairless Rat
Authors: Hueber Frédérique , Wepierre Jacques , Schaefer Hans
Published: April 2009

The importance of the transappendageal route on percutaneous absorption was assessed in the hairless rat. Skin permeation of two steroids, hydrocortisone and testosterone, was evaluated in vivo on normal and artificially damaged skin in which follicles and sebaceous glands disappeared during healing. The test compounds were applied for periods of 0.5,2 and 6 h. Thereafter, the stratum corneum reservoir function, the epidermal and dermal distribution profiles, and systemic absorption were determined for both molecules. The results presented here show that the reservoir function of the stratum corneum of appendage-free (scar) skin is more pronounced than that of normal skin, whereas the concentration appearing in the epidermis and dermis was greater in normal skin. Moreover, sebaceous glands probably contribute to the penetration of hydrocortisone and testosterone. We show that the relative importance of the skin appendages depends on the intrinsic physical properties of the molecules tested, and the time of application.
Interaction of Minoxidil with Pigment in Cells of the Hair Follicle: An Example of Binding without Apparent Biological Effects
Authors: Buhl Allen E. , Kawabe Thomas T. , MacCallum Donald K. , Waldon Daniel J. , Knight Karen A. , Johnson Garland A.
Published: April 2009

To identify minoxidil target cells in hair follicles we followed the uptake of radiolabeled drug in mouse vibrissae follicles both in vitro and in vivo. Autoradiography showed that both 3H-minoxidil and 3H-minoxidil sulfate accumulated in the differentiating epithelial matrix cells superior to the dermal papilla, a distribution similar to that of pigment. Minoxidil localized in melanocytes, melanocyte processes, and areas of greater melanin concentrations within the epithelial cells. Although uptake of minoxidil was significantly less in unpigmented follicles, the drug stimulated proliferation and differentiation of both pigmented and unpigmented follicles. Labeled minoxidil bound to Sepia melanin and was displaced with unlabeled minoxidil and other electron donor drugs. This interaction with melanin acts as a targeting mechanism of minoxidil to pigmented hair follicles but has no apparent functional significance in hair growth. This work illustrates how measurement of drugs in hair may be biased by pigmentation.
Assessment of Topical Corticosteroid Activity on Experimentally Induced Contact Dermatitis: Echographic Evaluation with Binary Transformation and Image Analysis
Authors: Seidenari Stefania , Di Nardo Anna , Giannetti Alberto
Published: April 2009

A new echographic evaluation method employing a B scanner and a dedicated software (Dermavision 2D, Cortex Technology, Hadsund, Denmark) was used in assessing the potency of three different corticosteroids. Experimental lesions were induced by patch tests with nickel sulfate 5 % in petrolatum in 10 sensitized subjects and treated with two medications of different steroids (clobetasol propionate, fiuocinolone acetonide or clobe-tasone butyrate) performed 16 and 40 h after the application of the nickel patch tests. Clinical and echographic evaluations were carried out at the beginning of the experiment and 64 h after the induction of the reactions. After obtaining echographic images, these were processed by software, enabling the selection of amplitudes of interest, the highlighting of parts of images and their assessment by a value corresponding to the number of pixels (picture elements). For evaluations a low reflecting band was chosen, marking edema and inflammatory infiltration. At positive patch test sites we observed a progressive increase in the number of low reflecting pixels, in accordance with the intensity of the reaction. Therapeutic response was assessed as the difference between values of treated and untreated test sites. The rank order of the efficacy of test substances as determined echographically was identical to the rank order generally accepted for these steroids. This evaluation method of topical corticosteroid activity could be usefully employed besides traditional evaluation methods.
Measurement of Color Parameters of Psoriatic Plaques by Narrow-Band Reflectance Spectrophotometry and Tristimulus Colorimetry
Authors: Takiwaki Hirotsugu , Serup Jørgen
Published: April 2009

Color parameters were measured on 50 psoriatic plaques in 10 patients, after scoring the amount of scales on them by inspection, with a narrow-band reflectance spectrophotometer (erythema/melanin index expression) and tristimulus colorimeter (CIE L*a*b* expression). Both erythema index and a* (redness) were highest in the group of erythematous plaque with little scale (twice as high as in controls) and decreased significantly as the plaques were covered with thicker scale, while L* (brightness) changed in just the opposite fashion of a*. These portable ‘color indicators’ can be utilized to express the appearance of psoriatic plaques quantitatively, especially the extent of erythema and the amount of the scale on it.
Chronic Topical Application of All-trans-retinoic Acid in Man Does Not Affect Corneocyte Surface Area
Authors: Robinson S.M. , Poncet M. , Ferracin J. , Czernielewski J. , Verschoore M.
Published: April 2009

The potential therapeutic activity of topically applied novel analogues of retinoic acid is currently measured in many different animal models. In most cases, the technique used is invasive and biopsy specimens are required. Furthermore, efficacy in these models is not a guarantee of success in treatment of humans. Therefore, predictive human pharmacology tests are required in order to quantify a retinoid effect on human skin before conducting large clinical trials. The aim of this study was to determine whether changes in corneocyte surface area could be used as a predictive measure for the efficacy of topical retinoids in man. Topical applications of all-trans retinoic acid gel (Aberel®), salicylic acid gel and the gel vehicle were made once daily for 4 weeks to skin of the lumbar region of healthy human volunteers. Corneocytes were recovered from these three treated zones as well as from one zone of untreated skin, and their surface areas were measured by image analysis using a MOP-Videoplan. The results showed that at no point during the 4 weeks of daily application to healthy human skin was there a statistically significant difference in the surface area of corneocytes recovered from Aberel, salicylic acid-, vehicle-treated or untreated sites. No specific effect of retinoic acid could be detected. However, although no between-treatment differences were found, significant cyclical changes in the mean surface areas with respect to baseline were observed.
Influence of Application Time and Formulation Reapplication on the Delivery of Minoxidil through Hairless Mouse Skin as Measured in Franz Diffusion Cells
Authors: Tsai J.-C. , Flynn G.L. , Weiner N. , Ferry J.J.
Published: April 2009

Relationships are drawn between the extent of topical delivery of test compounds in solution and the period of residence of their formulation on the skin. The studies were performed using in vitro diffusion cell techniques and a test formulation containing 2% 3H-minoxidil dissolved in 60% ethanol, 20% water and 20% 14C-propylene glycol. The permeation of pro-pylene glycol was effectively halted upon cleansing the skin surface; the skin had very little reservoir capacity for this substance. However, the rate of delivery of minoxidil was only slowed but not stopped upon cleansing. The suggestion here is that a reservoir of minoxidil is formed in the skin which is capable of sustaining an appreciable input of drug even after the skin’s surface is scrupulously cleaned. Assay of epidermal concentrations of these species not only confirms the existence of the minoxidil reservoir but also shows that the degree of its tissue concentration is proportional to the time of residence of the formulation on the skin surface. Reapplication of blank vehicle to the cleansed surface had little to no effect on the permeation of the minoxidil and was similarly without effect on that of propylene glycol. While it comes as no surprise that formulation residence time is an important variable in topical delivery, this study demonstrates the complexities of quantitative dependencies of delivery on residence time.
Echographic Evaluation with Image Analysis of Histamine-lnduced Wheats
Authors: di Nardo Anna , Seidenari Stefania
Published: April 2009

10 healthy, non-atopic women, aged 20–30, underwent histamine prick tests, performed in duplicate on the volar surface of the forearm with progressively increasing histamine concentration, from elbow to wrist on the left arm and from wrist to elbow on the right. Histamine wheal assessments were performed with the following methods at 5, 10, 15 and 20 min from challenge: planimetry for wheal area determination, A-scanning for skin thickness evaluation and echographic image analysis for assessing skin edema corresponding to the hypo-echogenic area in the dermis. Wheal extension, skin thickness and edema of the dermis increase in time according to the histamine concentration. However, in response to the same concentration, regional variations consisting in greater wheal extension and dermis hypoechogenic areas were observed on proximal than on distal sites. Conversely, statistically significant differences were found between tests carried out on the right arm compared to those on the left regarding skin thickness. These variations have to be considered when interpreting data derived from pharmacological studies on the inhibition of histamine-induced reactions.
Measurement and Modulation of Cytochrome-P450-Dependent Enzyme Activity in Cultured Human Keratinocytes
Authors: Raffali F. , Rougier A. , Roguet R.
Published: April 2009

The metabolism of xenobiotics by the epidermis can be studied in vitro by using keratinocyte cultures. We present a simple and rapid method for determining the activity of cytochrome P450-dependent enzymes (ethoxycoumarin-O-de-ethylase, ECOD, and ethoxyresorufm-O-deethylase, EROD) in intact cultured human keratinocytes. Using this method, we studied the effect of a well-known cytochrome P450 inhibitor (proadifen) and of two inducers (phenobarbital and 3-methyl-cholanthrene). As reported in vivo some imidazole compounds (miconazole and econazole) induce ECOD activity at low concentrations and inhibit it at high concentrations. In contrast, two other imidazoles (clotrimazole and sulconazole) only had an inducing effect on ECOD activity. Imidazole itself had no apparent effect on ECOD activity. In conclusion, this model appears to be useful for studying the biotransforming activity of human skin. It allows a rapid evaluation of the inducing/inhibitory effects of xenobiotics.
Inhibitor of the Release of Mast Cell Mediators Does Not Improve the Psoriatic Plaque
Authors: van de Kerkhof P.C.M. , Goos M. , Christophers E. , Baudin M. , Dupuy P.
Published: April 2009

The number of mast cells is increased in psoriatic lesions and this is particularly prominent in their early phase. Mediators released by mast cells may interfere with various aspects of cutaneous inflammation and epidermal proliferation. Therefore, the aim of the present investigation was to find out whether a 4-week treatment period with Tiacrilast, a highly potent inhibitor of mast cell degranulation, might have anti-psoriatic potential. A total of 31 patients with plaque-type psoriasis were evaluated after treatment with a 3% Tiacrilast hydrogel and hydrogel alone, in a double-blind, placebo-controlled, within-patient comparative study. No statistically significant improvement of the Tiacrilast-treated plaques compared to the hydrogel-treated sites could be demonstrated. Therefore, the present study does not provide evidence of a potential role of mast cell degranulation in the treatment of psoriasis.
Differential Utilization of Linoleic and Arachidonic Acid by Cultured Human Keratinocytes
Authors: Schürer Nanna , Schliep Viola , Williams Mary L.
Published: April 2009

The essential fatty acid, linoleic acid (LA), is required for the epidermal barrier and LA is also the precursor fatty acid for arachidonic acid (AA). Both fatty acids are imported from systemic sources, because AA is also not synthesized in the epidermis. The present studies were undertaken to compare the uptake and incorporation into cellular lipid of these fatty acids and to determine whether they compete with one another in these processes in relation to keratinocyte differentiation. The incorporation of [I4C]LA and/or [14C]AA into phospholipids and triglycerides was examined in keratinocytes cultured under submerged and lifted conditions. In submerged (less well-differentiated) cultures, more LA was incorporated into phospholipids than AA, while AA was incorporated into triglycerides to a greater extent. When given together, neither fatty acid influenced the total and/or relative uptake and lipid distribution of the other. Compared to submerged cultures, the uptake of LA increased 2-fold in lifted (differentiated) cultures, while the uptake of AA was unchanged. Lifting increased the proportion of AA incorporated into phospholipids, but did not alter the distribution of LA among phospholipids or triglycerides. These data suggest that the essential fatty acids, LA and AA, which are destined for different metabolic roles within the keratinocyte do not compete with one another during their uptake and distribution among cellular lipid species. Furthermore, as keratinocytes differentiate in culture, their increased requirement for LA for the synthesis of barrier lipids may be achieved through the preferentially enhanced uptake and lipid incorporation.
Modelling of Drug Penetration into Human Skin Using a Multilayer Membrane System
Authors: Neubert Reinhard , Wohlrab Wolfgang , Bendas Christina
Published: April 2009

In this article, a new in vitro model system is presented with a multilayer membrane system serving as acceptor. Matrix-stabilized membranes are applied with dodecanol as lipid and collodion as matrix. Using the drug dithranol it was shown that the acceptor system can be varied over a wide range by changing the dodecanol content of the membranes and by addition of the hydrophilic substance propylene glycol to the membranes. It was demonstrated that the variability of the acceptor system can be used to adapt the penetration profiles of dithranol in a six-layer membrane system to those in excised human skin. It is shown that it is possible to study the penetration of dithranol from different semisolid formulations using the ‘adapted’ model system.
Treatment of Porphyria cutanea tarda by the Effect of Chloroquine on the Liver
Authors: Freesemann Anne , Frank Margareta , Sieg Ina , Doss Manfred O.
Published: April 2009

Porphyria cutanea tarda (PCX) is characterized by cutaneous symptoms in association with hepatic accumulation and urinary excretion of mainly uro- and heptacarboxyporphyrins. 24 PCX patients excreting urinary porphyrins between 1.9 and 5.8 µmol/24 h (normal < 0.2) were treated with chloroquine at a dose of 125 mg twice a week. During the first phase of therapy urinary porphyrin excretion transiently increased 1.1- to 2.9-fold indicating a phase of mobilization. A slight initial elevation was also found regarding the activities of serum amino-transferases reflecting the hepatotoxic effect of chloroquine. Xhe clinical symptoms disappeared after a period ranging from 2 to 6 months, and after an average of 12 months the porphyrin excretion in all patients had returned to nearly normal values.
Effects of Human Recombinant Interferon-α2b on P450-Dependent Isozymes in Rat Liver and Skin
Authors: Goerz G. , Tsambaos D. , Schuppe H.-C. , Bolsen K. , Georgiou S. , Reinauer S. , Zografakis Ch.
Published: April 2009

Adult female Wistar rats divided into two groups (6 animals each) were subcutaneously treated with 105 units/day recombinant human interferon-α2b (hrIFN-α2b) and corresponding quantities of the vehicle, respectively, over a period of 7 days. Microsomal protein, P450 content, and the activities of ami-nopyrine-N-demethylase (ADM), 7-ethoxyresorufm-O-de-ethylase (7-ERO-D) and of erythromycin-N-demethylase (EMDM) were determined in the liver microsomes. Moreover, 7-ERO-D and EMDM activities were determined in the skin microsomes of the treated animals. In the liver microsomes hrIFN-α2b caused a statistically significant increase in ADM activity and a statistically significant decrease in 7-ERO-D and EMDM activities, as compared to the controls. However, in the pooled skin microsomes 7-ERO-D activity showed a trend to increase under the administration of hrIFN-α2b, whereas EMDM activity could not be detected in the treated or the control animals. The results of the present study indicate that hrIFN-α2b is capable of affecting the activities of P450-dependent isozymes in the rat liver and skin in a different manner. Our findings support the hypothesis that clinically relevant interactions may occur during the concomitant administration of hrIFN-α2b and other compounds that are metabolized by hepatic and cutaneous P450 monooxygenases.
Regulation of Cellular Retinoic Acid Binding Protein Expression in Rhino Mouse Skin by All-trans-Retinoic Acid
Authors: Gendimenico Gerard J. , Mallon John P. , Cromie Matthew A. , Mezick James A. , Åström Anders , Elder James T.
Published: April 2009

Cellular retinoic acid binding proteins (CRABP) are cytoplasmic proteins that bind all-trans-retinoic acid (RA) and other retinoids. The purpose of these studies was to determine the effects of topically applied RA on CRABP expression in rhino mouse skin. CRABP-II mRNA was significantly induced (3-to 4.5-fold) by a single dose of RA at 6 and 16 h after RA treatment, with a return to control levels at 48 h. CRABP-II message was not significantly elevated by 3 or 4 consecutive days of RA treatment, when assessed 24 h after the last treatment. CRABP-I mRNA was undetectable in control and RA-treated skin. We used radiolabelled RA binding combined with non-denaturing PAGE blot autoradiography to distinguish the CRABP subtypes. By this protein assay method, increases in CRABP-II were detected 24 and 48 h after a single application of RA, as well as after 3 and 4 days of RA treatment. RA treatment did not alter CRABP-I expression relative to the vehicle control. These results demonstrate that in mouse skin CRABP-II, but not CRABP-I, is inducible by RA, and is similar to how RA regulates CRABP in human skin.
The Effect of Topical Steroid on the Actions of Vasoconstrictor and Vasodilator Peptides in Human Skin
Authors: Goldsmith Portia , Bunker Christopher , Leslie Tabi , Foreman John , Dowd Pauline M.
Published: April 2009

The effect of topical application of clobetasol propionate ointment (0.05% w/v) on the vascular changes induced by intradermal injections of histamine, calcitonin gene-related peptide, substance P, endothelin-1 and compound 48/80 was studied. Clobetasol propionate ointment was applied topically under occlusion to the forearm skin of healthy volunteers and vehicle base was applied to the contralateral forearm. The intradermal injections were made 4 h or, in a separate study, 72 h after topical steroid application. Responses were measured by planimetry and laser Doppler flowmetry. Four hours application of steroid did not significantly alter the responses to any of the vasoactive substances. After 72 hours application, clobetasol propionate significantly increased the size of the endothelin-1-induced area of vasoconstriction (p < 0.02) and significantly reduced the size of the flares induced by endothelin-1 (p < 0.02), substance P (p < 0.009) and compound 48/80 (p < 0.05). We conclude that the most likely explanation of our data is an inhibition by the steroid of cutaneous mast cell function.
The Effect of Lowered Body Temperature on Lifespan and Immune and Non-Immune Processes
Authors: Liu R.K. , Walford R.L.
Published: April 2009

The effect of lowered body temperature on lifespan and immune and nonimmune processes in invertebrates and vertebrates are reviewed. Decreasing the environmental temperature tends to increase lifespan of invertebrates and poikilothermic vertebrates. Thermolabile homeotherms appear to live longer than comparably-sized species which do not undergo periodic, natural lowering of their body temperature. Even a mild lowering of temperature suppresses both humoral and cellular immune processes in poikilotherms. On the other hand, metabolic and biochemical responses to decreased body temperature in poikilotherms are quite varied. With mild or moderate hypothermia (30–35°C), indications are that for most homeotherms, there would not be a major inhibition of nonimmune biochemical or metabolic processes. Initial studies aimed at inducing mild, chronic or intermittent hypothermia in mice with chloropromazine and marihuana derivatives are described.
Aging: Alteration of DNA-Protein Information
Authors: Price G.B. , Makinodan T.
Published: April 2009

The techniques behind the investigation of freeradical, somatic mutation, and DNA-protein deterioration theories are no longer adequate to further our knowledge significantly on the role of DNA-protein complexes in aging dysfunction. Clearly, only the preliminaries were accomplished by studies based on the hypotheses of DNA-protein interactions for aging. As we see it, we urgently need to address ourselves to one simple question at a time, specifically to age changes in the DNA-protein complex, a potential site of primary changes leading to aging dysfunction.
3D gravity inversion through an adaptive-learning procedure
Authors: Silva Dias Fernando J. , Barbosa Valéria C. , Silva João B.
Published: April 2009

We have developed a gravity inversion method to estimate a 3D density-contrast distribution producing strongly interfering gravity anomalies. The interpretation model consists of a grid of 3D vertical, juxtaposed prisms in the horizontal and vertical directions. Iteratively, our approach estimates the 3D density-contrast distribution that fits the observed anomaly within the measurement errors and favors compact gravity sources closest to prespecified geometric elements such as axes and points. This method retrieves the geometry of multiple gravity sources whose density contrasts (positive and negative values) are prescribed by the interpreter through the geometric element. At the first iteration, we set an initial interpretation model and specify the first-guess geometric elements and their target density contrasts. Each geometric element operates as the first-guess skeletal outline of the entire homogeneous gravity source or any of its homogeneous parts to be reconstructed. From the second iteration on, our method automatically redefines a new set of geometric elements, the associated target density contrasts, and a new interpretation model whose number of prisms increases with the iteration. The iteration stops when the geometries of the estimated sources are invariant along successive iterations. Tests on synthetic data from geometrically complex bodies and on field data collected over a mafic-ultramafic body and a volcanogenic sedimentary sequence located in the Tocantins Province, Brazil, confirmed the potential of our method in producing a sharp image of multiple and adjacent bodies.
A simplified model of effective elasticity for anisotropic shales
Authors: Ougier-Simonin Audrey , Sarout Joël , Guéguen Yves
Published: April 2009

A simple method to deal with cracklike pores in anisotropic matrix rock such as shales enhances analytical models and their applications. Actually, clayrocks (shales, in particular) are the dominant clastic component in sedimentary basins, representing about two-thirds of all sedimentary rocks. Shales are usually assumed to be transversely isotropic (TI) media. They are known to be highly anisotropic because of (1) intrinsic elastic anisotropy of the solid phase (matrix) forming the rock (more or less ordered clay layers) and (2) anisotropy induced by the presence of cracklike pores. We focus on this second component of anisotropy. Current analytical models deal with it, but they are complex and are restricted in the case of matrix TI symmetry to cracks lying in the symmetry plane. We simplify such models within a reasonably good approximation and develop an analysis scheme in which cracklike pore effects are calculated in an equivalent isotropic matrix. This simplifies the theoretical approach and potentially broadens its application to any crack and/or pore orientation, e.g., damaged shale with horizontal and vertical (perpendicular to the bedding plane) cracks. A high-pressure confinement test provides experimental data for checking the proposed tool against a reference model in the case of cracklike pores lying in the bedding plane. The results (in terms of Thomsen parameters) are consistent with results from large-scale field data.
Restriction of Fourier transforms to curves and related oscillatory
integrals
Authors: Bak Jong-Guk , Oberlin Daniel M. , Seeger Andreas
Published: March 2009

We prove sharp endpoint results for the Fourier restriction
operator associated to nondegenerate curves in ${\Bbb R}^d$, $d\ge
3$, and related estimates for oscillatory integral operators.
Moreover, for some larger classes of curves in ${\Bbb R}^d$ we
obtain sharp uniform $L^p\to L^q$ bounds with respect to affine
arclength measure, thereby resolving a problem of Drury and
Marshall.
Gradient flows on Wasserstein spaces over compact Alexandrov spaces
Authors: Ohta Shin-Ichi
Published: March 2009

We establish the existence of Euclidean tangent cones on Wasserstein
spaces over compact Alexandrov spaces of curvature bounded below. By
using this Riemannian structure, we formulate and construct gradient
flows of functions on such spaces. If the underlying space is a
Riemannian manifold of nonnegative sectional curvature, then our
gradient flow of the free energy produces a solution of the linear
Fokker-Planck equation.
F-injective singularities are Du Bois
Authors: Schwede Karl
Published: March 2009

In this paper, we prove that singularities of $F$-injective type are
Du~Bois. This extends the correspondence between singularities
associated to the minimal model program and singularities defined by
the action of Frobenius in positive characteristic.
The first sign
change of Fourier coefficients of cusp forms
Authors: Choie YoungJu , Kohnen Winfried
Published: March 2009

Let $f=\sum_{n>o} a(n)q^{n}, a(n)$ real, be an arbitrary nonzero
cusp form of even integral weight $k\geq 2$ on $\Gamma_0(N),$ square
free $N.$ We obtain an effective bound that the first sign change of
$a(n)$ occurs.
The Collaborative Roles of the Designer, the Marketer, and the Consumer in Determining What is Good Design
Authors: Garber Lawrence L. , Hyatt Eva M. , Boya Ünal Ö.
Published: March 2009

The past view of the artist or designer as a uniquely talented visionary whose own references are mainly internal has migrated to that of communicator. With respect to product design, we are in the midst of a move to a much more consumer-oriented practice by which the needs of the consumer and her or his response to products in the midst of the design process are solicited and factored into the whole process much more assiduously than ever before. The flow of communication between designer and consumer has transformed from a largely one-way process (from artist to receiver) to a much more interactive process involving the marketer as intermediary. This change includes a shift from the traditional modes of marketing communications, characterized as a one-way flow of information from sender to receiver, to a collaboration between the marketer and consumers. This feedback from the marketing research process concerning the usefulness and acceptance of various designs is now a well-established, micro-level feedback loop. In the following we propose an additional, macro-level loop that also feeds back to the designer and also influences the creative process. Though it may be a latent process, and less deliberate, it contributes to the designer’s sensibilities in a manner that may not be so apparent to the designer. This loop is mediated by consumer feedback once again, though not by individual responses to market researchers deliberately made to designers during the design process, or by their individual purchases, but by collective consumption and usage patterns. Those products, packages, and advertising imageries that prove popular proliferate into our world to serve as visual background to our daily lives. In the following, we examine the role of each player in detail.
Jameson's Modernisms; or, the Desire Called Utopia
Authors: Wegner Phillip E.
Published: March 2009

This essay offers an immanent reading of Fredric Jameson’s Archaeologies of the Future (2005) in terms of his theorization of a four-fold allegorical hermeneutic. On the literal level, the book explores science fictions; on the allegorical, Utopian representations; on the moral, or individual psychological, it serves as a “partial summing up” of a number of sequences in Jameson’s ongoing project; and on the anagogical, it contributes to a reinvention of Marxism for an era of globalization. Jameson’s recent writings also share an interest in modernism, challenging late modernist ideology and recovering more radical forms. The essay concludes by exploring how Jameson’s discussion of Utopia serves as a figure for the problems of radical politics in the present.
The Literary Thing
Authors: Macherey Pierre , Wasser Audrey
Published: March 2009

The polysemy of the expression "the literary thing" draws our attention to an ambiguity and a tension at the heart of our conception of literature. Between its essence and its existence, its invocation of timeless ideals and its participation in worldly matters, its celebration of genius and its reliance on the minor writing that makes up the ordinary and continuous weft of literary production, literature is at least two things at once, between which we have not finished going uncertainly back and forth. The "literary thing" is the difficult cohabitation of these aspects, which seem to exclude one another yet are inseparable.
Futures of Literature: Inhitat, Adab, Naqd
Authors: Sacks Jeffrey
Published: March 2009

This essay traces the historicity of a single non-European literary critical idiom by addressing the modes in which “founding” and “subsequent” texts in literature and in criticism both form and interrupt the possibility of speaking of literature as an object. Focusing upon selected writings of Butros al-Bustani (1819–83) and Muhammad al-Muwaylihi (1858–1930), this essay considers the separations that attend the institutionalization of Arabic literary studies—between the old and the new, the modern and the classical, the secular and the religious, and more—and that give literature to appear as an object of study even as they compel what is more idiomatic in literature to withdraw and disappear.
Views from Above and Below: George Eliot and Fakir Mohan Senapati
Authors: Sawyer Paul
Published: March 2009

By reading a novel by George Eliot alongside a novel by her Indian contemporary Fakir Mohan Senapati, this essay offers a cross-cultural comparison of fictional realisms. In
The Mill on the Floss (1860), Eliot used a learned narrator and extended forms of free indirect discourse to examine humble life with unprecedented sympathy and complexity, but the formal dissonance between the authoritative narrative voice and class-marked forms of represented speech construct a view of the lower classes from “above”—that is, from the vantage point of the educated middle-class readers whom Eliot implicitly constructs as the agents of history. By contrast, Senapati’s Six Acres and a Third (1897–99), written in the demotic Indian language of Oriya, achieves a view from “below” through an ironic narrator who parodies the very type of learned discourse that Eliot (at the opposite end of the British empire) deploys as the instrument of liberal humanism. By thus evacuating a discursive cultural authority, Senapati produces a dialogic interplay of voices that brings the reader into the lives of his impoverished villagers without sentimentality or condescension—an achievement that in some ways resembles later European modernism as much as the realism of Eliot.
Unionization: A Private Sector Solution to the Economic Crisis
Authors: Payne Michael
Published: March 2009

One of the most important solutions to the current economic crisis is a bill that, outside the labor movement and antilabor
business lobbies, almost no one has heard of: the Employee Free Choice Act, which would make it easier for
American workers to form unions. The EFCA would not increase public spending by a cent or add a single bureaucrat
to the federal government. It would not impose new regulations on business, nor would it dictate anything about the
wages and benefits employers pay their workers. Yet it just might be the key to restoring the ability of American
workers to attain a modest, middle-class lifestyle.
One nation, off the clock
Authors: Brook Daniel
Published: March 2009

During the last presidential transition, George W. Bush made his first political misstep with the nomination of Linda Chavez for secretary of labor. A conservative columnist, Chavez had a long paper trail of arguing that the “glass ceiling” didn’t exist and calling women who bring workplace sexual harassment suits “crybabies.” But perhaps her most bizarre position of all was her opposition—on principle—to the minimum wage. Chavez subscribed to the Chicago School canard (debunked by empirical evidence) that minimum wages increase unemployment, hurting the very workers they are supposed to help.
Run-up: the road to Iraq
Authors: Mills Nicolaus
Published: March 2009

Since 2004, accounts of how the Bush administration maneuvered the country into war of choice in Iraq with the false
claim that Saddam Hussein possessed weapons of mass destruction have quickly made it on to the best-seller list. It
is easy to see why. While in power, Bush and his supporters often seemed indifferent to the charge that they had
invaded Iraq without having hard evidence of Saddam’s military capability. As Paul Wolfowitz, Donald Rumsfeld’s
deputy defense secretary, told the press in 2003, “The truth is that for reasons that have a lot to do with the U.S.
government bureaucracy, we settled on the one issue that everyone could agree on, which was weapons for mass
destruction as the core reason.”
Sheri Berman replies
Authors: Berman Sheri
Published: March 2009

Let me begin by thanking Joanne Barkan for her thoughtful comments. On many points we agree, but on several big
ones we do not—about the distinctiveness of the social democratic tradition, its superiority to other traditions on the
democratic left, and the requirements for the Left’s success today and in the future. Barkan is bothered by my linkage
of Michael Harrington’s work, and American politics more generally, to older European political debates. But that was
precisely the topic the editors of Dissent asked me to address—and it was a challenge I accepted because I do
believe there are striking similarities between the two and that the older stories I tell have contemporary relevance
and, in Barkan’s words, “apply to the Western world in general.”
Can we have universal health care?
Authors: Bybee Roger
Published: March 2009

Barack Obama aspires to be a “transformative” president, with his hopes particularly fixed on America’s finally
achieving a universal health care system. But would his health plan go far enough to transform a system that has been dominated and distorted by for-profit
insurers who maximize profit by rationing care to patients, restricting doctors' choice of treatments, and raising
premiums? Of course, the outlines of Obama’s plan will be profoundly changed by the legislative process, and it may
be virtually unrecognizable once a finished product reaches the presidential desk. But it is a valuable starting point for
discussing what is likely to succeed, and what is likely to fail, in health care reform.
Re-interpreting Ludlow
Authors: Green James
Published: March 2009

For all intents and purposes, the nation’s age of industrial violence ended with the Memorial Day massacre in South Chicago in 1937. During the previous fifty-year period, seven hundred deaths were recorded in industrial conflicts, though the actual body count was probably much higher. These grim facts mean that the United State experienced the bloodiest, most violent labor history of any industrial national in the world. During the past seventy years fatalities from other forms of workplace violence have continued to be all too common—more than 28,000 dead from workplace injuries between 2002 and 2007. But because violent strikes and shootings have been rare in recent times, the living memory of bloody labor repression is dying, along with the generation of workers who fought the bitter battles of the 1930s. It is now up to labor historians, union educators, preservationists, anthropologists, and filmmakers to keep those memories alive.
Losing ground: Another Look at Made in L.A.
Authors: Ross Robert J.S.
Published: March 2009

An inspiring if flawed documentary, Made in L.A. follows three Los Angeles sweatshop workers as their lawsuit
against a low-price retail label and the community campaign to support them developed from 2001 through 2004.
Enthusiastically received by critics and activists in 2007 when it was broadcast on PBS’s P.O.V. series, the film
received even more praise in 2008 when it won an Emmy for “Outstanding Continuing Coverage of a News Story-
Long Form.”
Departing responsibly
Authors: O’Leary Brendan
Published: March 2009

The political and military scene in Iraq is best described as a series of truces. All parties await America’s exit, and all will try to steer it
in their favor. President Barack Obama’s moment can be used either to guide Iraq toward a successful federation or to preside over a
failed transfer of power, one in which the United States, with bungled intentions, assists divided Arab centralists in Baghdad to go to
war with Kurdistan and with each other. Leaving Iraq with integrity requires the Obama administration to ensure a secure balance of power within Iraq. That is made feasible
by Iraq’s Constitution, properly understood. It also requires the new administration to encourage clear internal territorial demarcations
within Iraq’s federation, especially between Kurdistan and al-Iraq al-Arabi. It will have to inhibit fearful or aggrandizing interventions
by Iran or Turkey and the provisioning of insurgents by Sunni Arab-dominated states.