Three-dimensional evaluation of subclinical extension of extramammary Paget disease: visualization of the histological border and its comparison to the clinical border.

BACKGROUND: In extramammary Paget disease (EMPD), Paget cells are sometimes detected outside the clinical border (subclinical extension). However, the spreading pattern of Paget cells in subclinical extension remains unclear. In addition, the macroscopic appearances of lesions accompanied by subclinical extension are totally unknown. OBJECTIVES: To characterize the spreading pattern of Paget cells as well as the macroscopic appearance of lesions of EMPD with subclinical extension. METHODS: Nineteen patients with primary anogenital EMPD underwent mapping biopsies and excisional surgeries; biopsy samples were then taken at the periphery of well-demarcated lesions. Samples were transparentized and subjected to whole-mount immunostaining with anticytokeratin 7 antibody to label Paget cells. The histological border was evaluated in three dimensions by two-photon microscopy. The shape and location of the histological border were compared with those of the clinical border. RESULTS: In 21 samples taken at the lesion where subclinical extension was not shown by mapping biopsy, the shape and location of the histological border were almost identical to those of the clinical border. However, two samples exhibited small foci of Paget cells outside the clinical border, showing subclinically extended satellite lesions. In the two samples taken at the lesions where subclinical extension was shown by mapping biopsy, a continuous arrangement of Paget cells extending beyond the clinical border was identified. Subclinically extended Paget cells were detected solely outside hypopigmented patches with erythema. CONCLUSIONS: In EMPD, at least two patterns of subclinical extension exist: continuous and satellite lesions. Subclinical extension might exist preferentially outside hypopigmented patches with erythema.

Topical treatment with basic fibroblast growth factor promotes wound healing and barrier recovery induced by skin abrasion.

It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery.

Cholinergic urticaria: pathogenesis-based categorization and its treatment options.

BACKGROUND: Cholinergic urticaria (CU) has well-described characteristic clinical presentations, yet the precise pathological mechanism remains incompletely understood. A variety of pathogeneses has been proposed, which suggests that there exists several clinical subtypes. CONCLUSIONS: In this review, we categorize CU into four subtypes: (i) CU with poral occlusion; (ii) CU with acquired generalized hypohidrosis; (iii) CU with sweat allergy; and (iv) idiopathic CU, and discuss diagnostic and treatment options.

Wheatstone-Panum limiting case: occlusion, camouflage, and vergence-induced disparity cues.

We examined effects of binocular occlusion, binocular camouflage, and vergence-induced disparity cues on the perceived depth between two objects when two stimuli are presented to one eye and a single stimulus to the other (Wheatstone-Panum limiting case). The perceived order and magnitude of the depth were examined in two experimental conditions: (1) The stimulus was presented on the temporal side (occlusion condition) and (2) the nasal side (camouflage condition) of the stimulus pair on one retina so as to fuse with the single stimulus on the other retina. In both conditions, the separation between the stimulus pair presented to one eye was systematically varied. Experiment 1, with 16 observers, showed that the fused object was seen in front of the nonfused object in the occlusion condition and was seen at the same distance as the nonfused object in the camouflage condition. The perceived depth between the two objects was constant and did not depend on the separation of the stimulus pair presented to one eye. Experiment 2, with 45 observers, showed that the disparity induced by vergence mainly determined the perceived depth, and the depth magnitude increased as the separation of the stimulus pair was made wider. The results suggest that (1) occlusion provides depth-order information but not depth-magnitude information, (2) camouflage provides neither depth-order nor depth-magnitude information, and (3) vergence-induced disparity provides both order and magnitude information.

Subjective staircase: a multiple wallpaper illusion.

When observers binocularly fixate on an inclined sheet of paper with equally spaced dots, an apparent "staircase" is seen. We varied the inclination of the sheet, the spacing among the dots, and the viewing distance. The results indicate that (1) as the space and the inclination decreased, the number of apparent steps increased and the height of apparent steps decreased, and (2) as the distance and the inclination increased, the number of apparent steps decreased, and eventually the illusion disappeared. The nearest-neighbor rule and the extent of the vertical horopter inclination explain the characteristics of the illusion.

Visual directions of two stimuli in Panum's limiting case.

Visual directions of the two stimuli in Panum's limiting case with different interstimulus and convergence distances confirmed the predictions from the reformulated Wells-Hering's laws of visual direction. In experiment 1, six observers each converged on the midpoint of the interstimulus axis at 30, 60, and 90 cm from the eyes and adjusted a probe on the fixation plane to be in the same visual direction as that of each stimulus. Visual direction of the far stimulus was always nonveridical whereas that of the near stimulus was veridical only when its retinal disparity was small. In experiment 2, three observers each converged on the intersection of mid-sagittal plane and (a) the frontoparallel plane of the near stimulus, (b) that of the midpoint between the two stimuli, or (c) that of the far stimulus. The midpoint of the interstimulus axis was 60 cm from the eyes. Visual direction of the far stimulus was veridical only with convergence at the far plane. Visual direction of the near stimulus was veridical with convergence at the near plane, and also, only when its retinal disparity was small, with convergence at the two other planes.

[Recognition and categorization of butterfly patterns].

Two experiments are reported which deal with the nature of categorization of visual patterns. Stimulus materials were schematic butterfly patterns. Systematic transformations of five physical features (fore wing, hind wing, size, body length and color) were applied to a prototype to generate a set of instances. In Experiment 1, subjects were asked to judge the visual similarity between each instance and the prototype. Similarity ratings were found to be related to an each instance's transformational distance from the prototype. In Experiment 2, subjects were exposed to a subset of instances of the pattern which varied in their transformational distance from the prototype, and then given a recognition test with confidence ratings. The recognition item consisted of the old and new instances including the prototype. Recognition ratings were found to be related to each instance's family resemblance score rather than its transformational distance and subjective similarity to the prototype. These results support Rosch and Mervis's family resemblance model of categorization.

[The double-nail illusion revisited: commonality with the wallpaper phenomenon].

The double-nail illusion occurs when the images of two nails located at different distances from the observer fall on the corresponding retinal points, giving rise to the impression that the two nails are placed side by side at an equal distance from him. Experiment 1 showed that when two stimuli located on the mid-sagittal plane and at different distances were viewed in such a way that their images fall on the corresponding points, the perceived distance of the stimuli corresponded to the convergence distance. In Experiment 2, the convergence distance was changed gradually to get the measure of the distances at which the double-nail illusion appeared or disappeared. The results indicated the same kind of hysteresis as that previously observed in the 'dynamic' wallpaper phenomenon. Experiment 3 demonstrated the "double" wallpaper illusion, in which two wallpaper stimuli located in two different frontal-parallel planes appeared in a plane between the two and parallel to them. It showed moreover that the perceived distance of the wallpaper stimuli corresponded to the perceived distance obtained in the case of the double-nail illusion. The results of the three experiments indicated the commonality of the double-nail illusion with the wallpaper phenomenon and suggested that they share the same underlying perceptual processes. The principles of egocentric visual direction and distance were discussed with respect to the results.

[Fusional vergence hysteresis and sensorimotor connection of the two eyes].

Three experiments were conducted to replicate and extend Helmholtz's observation indicating vergence hysteresis. The two stimuli were presented dichoptically to the eyes in the mirror stereoscope and moved temporalward or nasalward. Helmholtz's finding was confirmed in Experiment 1, in which the critical separations were measured for the stimuli divergently moving temporalward when fusion of their images was abruptly broken (breakaway point) and when fusion was re-established (refusion point) for the stimuli moving nasalward. In Experiment 2, in which only the stimulus for one eye moved temporalward while the stimulus for the other eye was stationary, the breakaway point of the moving stimulus was found to be linearly dependent on the position of the stationary stimulus. Experiment 3 showed that, in the asymmetric divergent tracking as in Experiment 2, the change of the perceived visual direction of the fused image was smaller than the angular magnitude of the movement of the tracking eye. These results were discussed as evidence indicating the sensory and motor connection of the two eyes.

[Pulfrich stereoeffect during tracking eye movements].

An experiment was conducted to compare the magnitudes of the Pulfrich stereoeffect under two viewing conditions: fixating a stationary point and tracking a moving target. Three different transmittances of ND filters were used for each condition. The null method was employed to estimate the magnitude of the stereoeffect, in which the apparent depth was "nulled" by adjusting the physical depth of the target moving in an elliptical path in the eye-level horizontal plane so that no depth was seen. The results obtained from two experienced subjects showed that: the stereoeffect increased as the transmittance of the filter was decreased, and the stereoeffect was larger in the tracking condition than in the fixating condition for all three transmittances of the filters. The results were discussed within the context of depth information available for the visual system.

[Dynamic wallpaper phenomenon and fusional hysteresis].

Two experiments were conducted with six and three subjects, respectively, to examine the "dynamic" wallpaper phenomenon in which the apparent location of a uniform repeating pattern shifted abruptly at a certain convergence distance when the pattern was viewed with the gradual change of convergence. Experiment 1 demonstrated that the critical convergence distances (shift points), at which the apparent location of the pattern shifted, differed between the two directions of the change of convergence, converging and diverging. It was greater in the diverging condition than in the converging condition. This fact shows a tendency to keep the same fusional state as far as possible when the convergence changes gradually. Experiment 2 showed that the difference of the critical convergence distance between the converging and diverging conditions is systematically related to the convergence level, that is, the difference increased as the convergence angle increased. The implications of the results of the two experiments were discussed in the context of the fusional hysteresis.

[Psychophysical and vergence responses of normal and stereoanomalous observers to pulse-disparity stimulus].

The relations between psychophysical and oculo-motor responses to retinal disparity were examined in two experiments. Experiment I examined the subject's discriminability of the depth produced by 2 degrees crossed, 2 degrees uncrossed, and zero disparities with the durations of 100 and 1000 ms. As a result, six stereonormal, one crossed stereoanomalous, and one stereoblind observers were identified. In Experiment II, eye movement responses of three subjects with the different types of stereoscopic vision to the disparity pulses were monitored by the photo-electric method. The results of Experiment II indicated that the normal observer showed normal vergence, the crossed stereoanomalous observer showed anomalous convergence, and the stereoblind observer did not show any vergences but saccadic movements. Several theoretical implications of the results are discussed.