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Vitiligo is an autoimmune disease of the skin causing disfiguring patchy depigmentation of the epidermis and, less commonly, hair. Therapeutic options for vitiligo are limited, reflecting in part limited knowledge of disease pathogenesis. Existing mouse models of vitiligo consist of hair depigmentation but lack prominent epidermal involvement, which is the hallmark of human disease. They are thus unable to provide a platform to fully investigate disease mechanisms and treatment. CD8(+) T cells have been implicated in the pathogenesis of vitiligo, and expression of IFN-γ is increased in the lesional skin of patients, however, it is currently unknown what role IFN-γ has in disease. Here, we have developed an adoptive transfer mouse model of vitiligo using melanocyte-specific CD8(+) T cells, which recapitulates the human condition by inducing epidermal depigmentation while sparing the hair. Like active lesions in human vitiligo, histology of depigmenting skin reveals a patchy mononuclear infiltrate and single-cell infiltration of the epidermis. Depigmentation is accompanied by accumulation of autoreactive CD8(+) T cells in the skin, quantifiable loss of tyrosinase transcript, and local IFN-γ production. Neutralization of IFN-γ with antibody prevents CD8(+) T-cell accumulation and depigmentation, suggesting a therapeutic potential for this approach.

Background Immune responses are largely regulated by cytokines that are secreted by activated T cells. Interactions among these cells are complex, and the interaction between 2 responses may alter the effect of either response alone. It has been established that contact sensitization–induced inflammation can reverse hair loss due to alopecia areata. In parallel, the Renbok phenomenon demonstrates how 2 distinct autoimmune diseases—psoriasis and alopecia areata—interact to result in clinically active psoriasis suppressing alopecia areata. Observations We describe a patient with concurrent psoriasis and alopecia universalis with terminal hairs within plaques on his extremities, representing the only normal hair growth on his body. Adjacent biopsy specimens confirmed our clinical suspicion of plaque psoriasis with normal hair follicles and alopecia universalis with a peribulbar lymphocytic infiltrate. Our patient's psoriatic plaques cleared rapidly with narrow-band UV-B phototherapy, but hair growth at the site was maintained. His scalp alopecia responded to squaric acid dibutylester contact sensitization therapy. Conclusions This case represents a natural experiment in which 3 distinct but overlapping immune responses favored psoriasis or contact dermatitis over alopecia areata. The precise mechanism responsible for these effects remains unclear; however, based on recent reports, we speculate that cytokine cross-regulation plays a role in competition among these distinct immune responses.

Exophiala spinifera has been reported as an agent of cutaneous disease 18 times in the literature. Clinical presentations of cutaneous lesions vary widely, including erythematous papules, verrucous plaques, and deep subcutaneous abscesses. The clinical distribution and course of disease are also variable, depending on the age and immune competency of the patient. Histologic appearance occurs in one of two patterns - phaeohyphomycosis or chromoblastomycosis. While E. spinifera appears to be susceptible to multiple antimicrobial agents in vitro, clinical experience with treatment modalities has been variable. Prior to the availability of sequencing methods, species identification was based on the histopathologic presentation in tissue and morphologic features of the fungus in culture. It is likely that E. spinifera cutaneous infections have been underreported due to its incorrect identification based on earlier methods. We report an additional case of E. spinifera phaeohyphomycosis, the first to be definitively identified by sequencing. In addition, we summarize the variable clinical, histopathologic, and morphologic features, as well as treatment responses described in previously reported cutaneous infections caused by E. spinifera.

The structure, composition, thermal stability, and electrochemical reactivity of the chemisorbed layer formed when a clean and ordered Pd(111) electrode is exposed to a dilute solution of Na 2 S buffered at pH 10 have been studied. Under these adsorption conditions, the predominant solution species is the bisulfide ion, HS (aq) − . Experimental measurements were based upon low-energy electron diffraction, Auger electron spectroscopy, and thermal desorption mass spectrometry in conjunction with classical electrochemical methods. The bisulfide ion is oxidatively chemisorbed onto Pd(111) as zerovalent sulfur which forms a highly ordered structure upon slight heating, Pd(111) and coverage Γ = 1.07 ± 0.06 nmol cm 2 . This particular adiattice is thermally stable up to 1100 K, the highest temperature investigated, or up to 900 K in the presence of 10 −6 Torr of O 2(g) . On the other hand, it is easily oxidized electrochemically to aqueous SO 4 2− ions. Application of negative potentials has no effect either on the structure or the composition of this chemisorbed layer. However, if copious amounts of electrogenerated H 2(g) are present at the applied negative potentials, all the sulfur is hydrogenatively desorbed from the surface, most likely back to HS − (ag) species.

Etude des proprietes electrocatalytiques d'une electrode constituee soit d'un alliage d'or et de platine, soit d'une couche d'argent deposee sur du platine

Ag-specific immune tolerance results from the induction of cellular mechanisms that limit T cell responses to selective Ags. One of these mechanisms is characterized by attenuated proliferation and decreased IL-2 production in fully stimulated CD4+ Th cells and is denoted T cell anergy. We report the identification of the early growth response gene (Egr-2; Krox-20), a zinc-finger transcription factor, as a key protein required for induction of anergy in cultured T cells. Gene array screening revealed high Egr-2 expression distinctly persists in anergized but not proliferating murine A.E7 T cells. In contrast, Egr-1, a related family member induced upon costimulation, displays little or no expression in the anergic state. IL-2-mediated abrogation of anergy causes rapid depletion of Egr-2 protein. Full stimulation of anergic A.E7 T cells fails to enhance IL-2 and Egr-1 expression, whereas Egr-2 expression is greatly increased. Silencing Egr-2 gene expression by small interfering RNA treatment of cultured A.E7 T cells before incubation with anti-CD3 alone prevents full induction of anergy. However, small interfering RNA-mediated depletion of Egr-2 5 days after anergy induction does not appear to abrogate hyporesponsiveness to stimulation. These data indicate that sustained Egr-2 expression is necessary to induce a full anergic state through the actions of genes regulated by this transcription factor.

The implications of interferon effects on B-cell responses may impact both antimicrobial and autoimmune disease.

BackgroundThe zinc finger transcription factor EGR-2 has been shown to play an important role in the induction of T cell anergy and the regulation of peripheral T cell tolerance. In vitro, a prior study has show that T cells deficient in EGR-2 are hyperproliferative to IL-2 and produce elevated levels of the effector cytokine IFN-γ. EGR-2 deficient mice have increased levels of CD44(high) T cells in peripheral lymphoid organs, and with age, develop autoimmune-like features.Principal findingsHere we show that despite increased numbers of cells bearing an activated CD44(high)CD62L(low) phenotype, T cells from young healthy EGR-2 deficient mice have normal proliferative and cytokine responses, and the mice themselves mount normal immune responses against minor histocompatibility antigens, and the pathogens Toxoplasma gondii and lymphocytic choriomeningitis virus.ConclusionsOur results indicate that EGR-2 is not required to mount normal acute in vivo immune responses against foreign antigens, and suggest instead that it may serve to regulate the response to chronic antigenic exposure, such as that which occurs to autoantigens.

Several recent books and papers on memory have noted the passing of 100 years of memory research, taking 1885 as the starting date when Ebbinghaus published his experimental studies of memory. The study of memory has continued on a large scale and in recent times hundreds of research papers have been published each year.

The interaction of selected organic and inorganic functional groups, which are reversibly electroactive and strongly surface-active, with monometal (Rh, Pd, Ir, Pt, Au) and mixed-metal (Au-Pt, Ag-Pt) electrocatalysts has been studied to help establish the interfacial organometallic/coordination chemistry of these metals in aqueous solutions. Experimental measurements were based upon thin-layer electrochemical and ultra-high vacuum surface spectroscopic methods; the latter included low-energy electron diffraction, Auger electron spectroscopy, X-ray photoelectron spectroscopy and thermal desorption mass spectrometry. The results to date indicate the following trends: (i) Electrode surface phenomena can be modeled in terms of monometal and cluster coordination/organometallic chemistry. (ii) Chemisorption is analogous to oxidative addition; desorption is similar to reductive elimination. (iii) Chemisorption of an electroactive center favors its oxidized state over the reduced form. (iv) Chemisorption of electroinactive anionic reagents forms polyprotic surface acids. (v) Substrate-mediated interactions between pendant electroactive centers may arise if the redox group itself is surface-active. (vi) Substrate-mediated adsorbate-adsorbate interactions can be viewed similarly to mixed-valence complexes.

In two interview studies subjects were asked what memory aids they used and how often. In particular, the reported frequencies of use of external aids such as shopping lists and memos were compared with those of internal aids that have been investigated by psychologists, such as the method of loci. Subjects in the first study were 15 male and 15 female university students, and in the second, a group of 30 adult women, most of whom were housewives. In both studies the aids reported to be used most were external ones. However, it is pointed out that the most commonly used methods of remembering must be internal, although these are not usually considered to be aids. Some difficulties that arise in the assessment of memory in interview and questionnaire studies are discussed.

Lower lid stability can be affected by many conditions involving the lid directly, e.g. facial palsy, facial clefts, trauma, or tumors. Secondary stretching due to a poorly fitting orbital prosthesis can have the same effect. In 41 such eyelids, stability was obtained by inserting a large cartilage graft sutured to the tarsal plate and the infraorbital rim. Thirteen patients had tarsoconjunctival wedge resections, and 10 had lateral canthopexies performed at the same procedure. One graft was too small and was later replaced. There was one hematoma, which was evacuated. There were no other lid or visual problems. The follow-up is short, 21 months maximum, but so far the results are very satisfactory.

The study of the hydrochemistry of Western Port began in June 1973 as part of the Westernport Bay Environmental Study. The objectives were to understand nutrient dynamics and to assist in formulation of management guidelines for the bay and for use in mathematical modelling, Parameters measured included: inorganic forms of nitrogen, reactive phosphorus, total phosphorus, chlorophylls, dissolved oxygen, particulate and total organic carbon, salinity and reactive silica. Detailed sampling of Western Port waters was carried out every three weeks throughout the four-year period. Initially a 48-station grid was used, but as the study progressed this was expanded to 62 stations and 26 shore locations. Analyses of detailed salinity and reactive-silica distributions have revealed the major features of water circulation. Water moves around French Island in a clockwise direction and some recycling occurs off Tortoise Head to form a complete loop. A clockwise movement exists in the Western Entrance Segment while a weak counter-clockwise movement exists in the Rhyll Segment. An exchange period of about twelve weeks is indicated for waters in the upper parts of Western Port.

The surface electrochemical properties of Ag layers electrodeposited on smooth polycrystalline Pt electrodes has been investigated by observing the changes in the redox behavior of iodine chemisorbed on the bimetallic surface at critical stages of the electrodeposition process. It has been found that: (i) the electrochemical behavior of chemisorbed I at a given Ag coverage is the same whether deposition was performed before or after I adsorption; I is always the outermost layer. (ii) I − ( aq ) is oxidatively chemisorbed as iodine onto the electrodeposit regardless of Ag coverage. (iii) Chemisorbed iodine can be cathodically stripped from the Ag electrodeposit; the redox potential for the I( ads )/I − ( aq ) couple on Ag is shifted by about −1.5 V relative to that for the I 2 ( aq )/I − ( aq ) couple; the chemisorption strength of zerovalent iodine on Ag is 220 kJ mol −1 larger than that of I − . (iv) Deposition of 0.25 and 0.5 layer of Ag yielded results which could be rationalized in terms of I desorption from two chemisorbed states: one coordinated to Pt, the other to Ag. (v) Deposition of one layer of Ag exhibited unique I coverage vs potential plots which suggested that the bimetallic surface consisting of one Ag layer on Pt substrate possesses distinct interfacial properties. (vi) The redox behavior of I chemisorbed on two monolayers of Ag was very similar to those of bulk Ag, signifying that the surface chemistry of two monolayers of Ag is identical to that of the bulk material.

The relationship between memory performance in everyday life and performance on laboratory tests was investigated in a group of subjects with normal memory and two groups of severely head-injured subjects differing in time since injury (several months vs several years). Everyday memory was assessed using questionnaires and checklists completed by each subject and independently by a relative who was in daily contact with him. Overall, a high degree of consistency was found among these measures, though the lower consistency of the subjects' questionnaire illustrated the problems of validity with self-assessment. The relatives' questionnaire correlated with test performance for normal subjects and for the long-term head-injured group but not for the recently head-injured subjects who had not yet reached a stable state. The highest correlations were with prose recall and paired-associate learning. The absence of correlations with visual memory tests may have been due to low salience of visual errors in everyday life.

The oxidative addition and reductive elimination of the iodo ligand has been compared at smooth polycrystalline gold, platinum and iridium surfaces in aqueous solutions. On these three metals, the iodo species undergoes spontaneous oxidative chemisorption to form a close-packed monolayer of zero-valent iodine, the saturation coverage of which is limited by the van der Waals radius of the iodine atom; this oxidative addition process is further manifested by evolution of hydrogen gas from proton reduction. Elimination of iodine from these surfaces can be achieved by its reduction back to the anion either by application of sufficiently negative potentials or by exposure to ample amounts of hydrogen gas. On Pt and Ir, the reductive desorption of iodine is coupled with reductive chemisorption of hydrogen; consequently, the reaction is a two-electron, pH-dependent process. A plot of E 1/2 , the potential at which the iodine coverage is decreased to half its maximum value, against pH yields information concerning the redox potential of the I (ads) /I − (ads) couple in the surface-coordinated state. On Au, where dissociative chemisorption of hydrogen does not occur, the iodine-stripping process is a pH-independent, one-electron reaction. The difference in the redox potentials [ E o I(ads) - E o I(aq ] for the I (ads) and I 2(aq) /I − (aq) redox couples was found to be −0.90 V on Au, − 0.76 V on Pt, and −0.72 V on Ir. These values imply that the ratio of the formation constants for surface coordination of the iodine and iodide species ( K f,I / K f,I− ) is 2 × 10 28 on Au, 1 × 10 26 on Pt, and 2 × 10 25 on Ir.

The number distribution of particles between 0.02 and 8 μm was measured using a transmission electron microscope. The accumulative particle size distribution is given by the hyperbolic equation N = aD−b. Distribution of particles

The concentrations of suspended matter and particulate Cd, Cu, Pb and Zn were determined for 36 samples collected at 6 stations in the Antarctic Ocean during December, 1970 and January, 1971 using membrane filters. The concentration of suspended matter was determined gravimetrically and trace metal levels were determined using anodic stripping voltammetry. For waters deeper than 100 m the concentration of suspended matter was < 100 μg l−1. Concentrations up to 542 μg l−1 were recorded between surface and 100 m. Individual concentrations of the metals were scattered with depth. Average concentrations of particulate metals were: Cd, 3.5 ng l−1; Cu, 100 ng l−1; Pb, 35 ng l−1; and Zn, 230 ng ;l−1 These measurements represent non-steady state conditions of early Antarctic summer as the ice pack disintegrates and biological activity increases.

The mass distribution of total suspended matter was determined at 45 stations in the Gulf of Mexico using 0·45 μm membrane filters. In surface water, total suspended matter ranged from 600 μg/l. in the open Gulf to 2·4 mg/l. in near-shore waters. In water deeper than 100 m the range was 20 to 640 μg/l. A bimodal distribution was found which can not be completely explained; however, it appears that seasonal variations in primary productivity are important. The average value of total suspended matter for deep water was 166 μg/l., almost three times higher that the previously reported average.

Total suspended matter (TSM) has been determined by gravimetric analysis at nine stations in the Caribbean Sea. Vertical eddy diffusivities near the surface and bottom are calculated by applying a simplified diffusion equation to the mean vertical profiles of TSM. The eddy diffusivities range from 1 to 8 cm2/sec for the upper layer down to about 150 meters, but they are smaller in the bottom region up to about 80 meters from the bottom, ranging from 0.2 to 2 cm2/sec. Mid-depth (300 meters ∼1500 meters) maximum concentrations in the eastern stations are interpreted as advection of scouring at the sill depth of the Mona passage. The transport equation balanced with horizontal advection and vertical diffusion terms yields a solution that can be fitted to the vertical distributions near the mid-depth maximums, resulting in estimates of advection velocity of about 1 cm/sec and vertical eddy diffusivity of 5–10 cm2/sec.

Total suspended matter in the water column of the Caribbean was determined quantitatively by means of filtration through 0.45 μ membrane filters. Results show that prior values obtained by centrifuging methods are too low, and that the existence of a nepheloid layer cannot be gravimetrically demonstrated in the Caribbean.

Summary. 1 Diademodus hydei, a new genus and species of shark from the Cleveland Shale, is described and figured from the holotype in the Cleveland Museum of Natural History. 2 About 40 centimetres in length, the fish is an adult male with well-developed claspers; it shows a combination of hybodont and cladoselachian characteristics. 3 The teeth are many-cusped and bilaterally symmetrical, with the outer cusps longer than the inner; they approach more closely to the sculpturing of the scale pattern than in orther primitive sharks. 4 A comparison with the contemporaneous Cladoselache and Ctenacanthus clarki suggests that Diademdus is an early and not distant offshoot from the primitive chondrichthyan stock, the main line of which led through Ctenacanthus and the hybodonts to the modern elamobranchs; Cladoselache is a specialized side line of this main stock and is not an appropriate ancestral type for the Chondrichthyes.

A new method is described for vital staining of nervous tissue with methylene blue; it involves impregnation of whole embryos or tissue-fragments with the rongalitreduced dye under anaerobic conditions at pH5, followed by development of the stain in an oxygenated neutral saline solution. Determinations of the solubility of leucomethylene blue and experiments on vital staining with it and with the oxidized dye at different pH values are consistent with the hypothesis that the dye penetrates cell membranes and tissues mainly as the leucobase, but may pass along nerve (and muscle) fibres in the oxidized form. Penetration of the leucomethylene blue below pH5 is hindered by its ionization; above pH5 the penetration falls off because of reduced permeability of the cell membranes.

SummaryIn citrate-blood the erythrocytes undergo progressive swelling during storage at 2°C; this is reflected in the increase in the fragility to hypotonic saline solutions. This property is not reversible by washing in isotonic saline. Red cells stored in sucrose-citrate solutions shrink. Erythrocytes in 5.4% dextrose-citrate undergo rapid swelling which is due to the diffusion of dextrose and water into the cells. The process can be reversed by washing with isotonic saline. The addition of hypertonic dextrose solutions to blood-citrate produces hypertonic cell contents during storage. The transfusion of such cells results in intravascular hemolysis by action of the recipient's plasma. The osmotic activity of the erythrocytes thus becomes another criterion for the suitability of stored blood for transfusion. Blood collected in dextrose solutions should be chilled rapidly to avoid osmotic hemolysis during refrigeration.

Records of nearly 2000 dogfish collected from the Ilfracombe region suggest that the spawning season of this fish starts in November and continues at least until July. This area probably represents a spawning ground into which the females migrate during the spawning season; the males follow them much later in April and May.Figures are given to show the time taken at different temperatures for the embryo to develop to a series of definite morphological stages; these suggest that the temperature characteristic of the development (µ = 20,000) is substantially the same as for several teleost species.

It is suggested that vertical migration is an inescapable consequence of the use of light by planktonic forms as a means of attaining a level within the euphotic zone; no other sense organ appears capable of producing this result. The mechanism of light response in Daphnia fulfils the necessary requirements for vertical migration, and field observations on other species suggest the presence of similar if not identical physiological features in them. These features are a positive photokinesis which is combined with negative geotaxis at low light intensities; at a critical higher value of light intensity a typical dorsal light reflex cuts off the vertical rise. The dorsal light reflex is probably a response to illumination of the eye within the critical cone of submarine illumination, and is therefore not related to the direction of a particular light source such as the sun.

Seven hundred and fifteen perfusions were made into the eyes of 122 anesthetized living or dead cats via a catheter into the anterior chamber or via a catheter into the posterior chamber. The perfusion fluid was normal saline or Tyrode solution. At “steady state” condition the perfusion rate per unit of IOP was plotted against the IOP produced by the perfusion from IOP values of 20 mm Hg to values over 100 mm Hg. In living cats 48% of the resulting curves showed a rising slope and 15% showed a falling slope. In the eyes of dead cats 4% of the curves showed a rising and 68% showed a falling slope. In both living and dead cat eyes some curves were flat (i.e. showed no net slope), some were cup-shaped and some were dome-shaped. From July through January the ratio of rising slopes to falling slopes in the eyes of living cats changed gradually from 4 to 1·5. This change in experimental results appeared to correlate with the change in season and not with known factors associated with laboratory technique. No constant relationship was found between inflow perfusion rate and IOP in the eyes of living or dead cats perfused via either the anterior or posterior chamber.