The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study.

BACKGROUND: The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. OBJECTIVES: To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. METHODS: In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. RESULTS: No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50% at week 4 with CIM331 compared with -20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. CONCLUSIONS: A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone. CIM331 may become a novel therapeutic option for AD by inhibiting IL-31.

Low-dose prednisolone ameliorates acute renal failure caused by cholesterol crystal embolism.

AIMS: The prognosis of renal cholesterol crystal embolism (CCE) is poor. Although various treatments for CCE have been attempted, there is no optimal therapy. We tested the effect of low-dose prednisolone (PS) on CCE-related acute renal failure (ARF). PATIENTS AND METHODS: 7 patients (mean age 69 years) diagnosed with CCE-related ARF were treated with oral PS at 15-20 mg/day for 2-4 weeks, which was then tapered at 5 mg/day over 2-4 weeks, followed by 5 mg/day maintenance dose. Recurrent ARF during PS tapering was treated with a larger dose of PS. RESULTS: Inciting factors were identified in four patients: coronary angiography (n=3) and cerebral angiography (n=1). On admission, serum creatinine (SCr) was 2.1 +/- 0.3 mg/dl (mean +/- SEM). SCr and eosinophil count before treatment were 4.2 +/- 0.4 mg/dl and 682 +/- 73/microl, respectively. PS therapy improved ARF in all cases at week 2 (SCr 3.8 +/- 0.5 mg/dl) parallel to a decrease in eosinophilia (116 +/- 30/microl), and at week 4 (3.1 +/- 0.4 mg/dl and 134 +/- 20/microl, respectively). At last follow-up, renal function was improved or maintained in 5 patients compared with that at week 4 post-treatment. One patient died of lung cancer. Another required LDL apheresis and hemodialysis but died due to CCE-related multi-organ failure. A third patient had recurrent ARF and was re-treated with a larger dose of PS, which resulted in an immediate decrease in SCr. However, the patient developed acute renal dysfunction due to congestive heart failure, and required hemodialysis. CONCLUSIONS: Low-dose PS improved CCE-related ARF, probably through amelioration of inflammatory reaction surrounding affected renal vessels.

Intradermal administration of viral vaccines.

Intradermal administration maybe useful in lowering the cost of vaccination against hepatitis B significantly, and may also be helpful for the rapid induction of antibodies, reversing non-responsiveness, improving postexposure prophylaxis and immunising immunocompromised people. In addition, delayed type hypersensitivity skin reaction to the vaccine could serve as a useful marker for the acquisition of T helper type 1 immunoreactivity in vivo. However, there are some disadvantages when using intradermal vaccinations, including the requirement for skilful administration, the absence of approval from licensing authorities, the development of local skin reactions and a lower antibody response when 1/10 of the standard vaccine dose is used. This requires that appropriate vaccination regimens, including the correct vaccine dosage, and vaccination schedule are followed. In the future, a similar vaccination strategy might also be applied for the prevention and control of other infectious diseases. Copyright 1998 John Wiley & Sons, Ltd.

Scanning and transmission electron microscope study on the terminal blood vessels of the rat skin.

The microvasculature in the subepidermal layer of the rat foot was examined by scanning electron microscopy of corrosion casts and by transmission electron microscopy of serial ultrathin sections. Three-dimensional observation of the casts demonstrated that, in the walking pads (pressure areas) with a thick epidermis, terminal vessels formed tortuous capillary loops that penetrated vertically into well-developed dermal papillae. In other regions of the foot (non-pressure areas) with a thin epidermis, terminal vessels formed a horizontally arranged capillary network and each capillary of the network fitted into a shallow groove along the dermal epidermal boundary base. These differences in the pattern of vascular distribution might be of significance from the view point of the blood flow; in pressure areas, the vertically arranged, tortuous vessels might allow vertical mobility of the skin without injury to them and might keep the blood flow normal against the force of compression. In thin sections, however, capillaries of both the loops and networks were similar in spite of the differences in the vascular distribution and the architecture of the epidermal-dermal junction. Vessels located in close proximity to the epidermis exhibited endothelial fenestrations along their proximal margins. In vessels away from the epidermis, on the contrary, fenestrations were not apparent. Since endothelial fenestration is an anatomical property related to rapid material exchange, it may be concluded that the pattern of distribution and the fine structure of subepidermal capillaries adjusts to the metabolic needs of the epidermis.

Spontaneous architectural organization of mammalian epidermis from random cell packing.

The cells of the stratum corneum in the epidermis of some mammalian species are precisely stacked in columns in a honeycomb fashion. The epidermis constantly loses surface cells, which are replaced by basal cells that have differentiated during migration to the surface. The path of this migration is seen as precisely defined columns of cells that are in compressed Kelvin's tetrakaidecahedral form. We present a computer simulation of this architectural organization based on the assumption that the cells that migrate upward occupy less crowded regions. The simulation not only explained the mechanism by which the architecture is maintained during the process of cell replacement, but also showed that the architecture was spontaneously organized from initial cells supplied at random. Living organisms consist of self-organizing systems at various levels; however, self-organizing systems have been investigated mostly at the molecular level. The present computer simulation clarified the self-organizing system at the cellular level.

Degree of ultraviolet-induced tortuosity of elastic fibers in rat skin is age dependent.

To elucidate differential effects of ultraviolet (UV) exposure on three-dimensional networks of elastic fibers during maturation of rat skin, Sprague-Dawley rat hind limbs were irradiated with suberythemal doses of UV light (UVB, 130 mJ/cm2, or UVA, 27 J/cm2) in three different time courses of exposure: 3-9 weeks old, 9-15 weeks old, and 3-15 weeks old. Three-dimensional arrangement with special reference to linearity of elastic fibers was quantified by image analysis using a scanning electron microscope after a combination of intravascular resin injection and selective digestion technique using formic acid. Among the three irradiation groups, the group irradiated with UVB or UVA between 3 and 15 weeks old (UVB, three times per week; UVA, five times per week) elicited the most marked decrease in the linearity of elastic fibers. Despite the same irradiation period, there was a significant difference in the decreased linearity between the two irradiation groups of 3-9 and 9-15 weeks old, with the former irradiation group exhibiting greater loss of linearity than the latter irradiation group. The magnitude of the decreased linearity was greater in the UVB-exposed groups than in the UVA-exposed group. These findings indicate that the three-dimensional linearity of elastic fibers is more susceptible to disruption by UV exposures during the growth period than that after the growth period.

Differing cell surface distribution of human leukocyte antigen-DR molecules on epidermal Langerhans cells and eccrine duct cells.

Scanning electron microscopy (SEM) with immunogold labeling was employed to observe the undersurface of the human epidermis after it was split from dermal connective tissue, in an attempt to localize the molecules actually expressed on cell/tissue surfaces. We found that human leukocyte antigen-DR (HLA-DR) molecules were expressed on the surfaces of eccrine duct cells as well as those of epidermal Langerhans cells (LC) in normal skin. HLA-DR molecules, visualized by the deposition of gold particles, were distributed evenly on the LC surface but were present only along the interdigitating borders of the individual duct cells, thus producing a meshwork pattern on the duct surface. Transmission electron microscopy confirmed that the gold particles labeling cell surface HLA-DR molecules were seen only on the portions of duct cell membranes the interdigitated with neighboring duct cells. These findings suggest that the function of HLA-DR molecules may vary with their location and distribution. On the LC surface, the evenly distributed molecules seem to be well suited for promoting "accessory cell" functions. On duct cell surfaces, the HLA-DR molecules present along the intercellular spaces may be involved in trapping various peptide antigens that pass into the sweat gland filtrate and then are reabsorbed by the excretory duct, since these molecules have a highly permissive capacity for binding various peptides.

Angiocentric immunoproliferative lesions of the skin show lobular panniculitis and are mainly disorders of large granular lymphocytes.

Eleven patients with angiocentric immunoproliferative lesion (AIL) of the skin were studied. Histologically, three patients were grouped into AIL grade II (AIL-II), whereas eight showed angiocentric lymphoma (AIL-III). All the patients' specimens exhibited lobular panniculitis. Infiltrating atypical lymphocytes in nine patients possessed electron-dense membrane bound granules in electron microscopy. Phenotypically, the lymphoid cells in the AIL-II patients were positive for CD3 epsilon; two of these showed a positive reaction to CD2, CD7, and CD8, but lacked natural killer-associated (NKa) antigens CD16, CD56, and CD57. In six AIL-III patients, lymphoma cells were positive for CD2 in all patients, CD56 in five, CD3 epsilon in four, CD7 in four, interleukin-2 beta receptor in four, a pore-forming protein in four, and CD30 in three patients. The remaining two AIL-III patients had B-cell lymphoma. By the Southern blot analysis, three patients with AIL-III showed a rearranged T-cell-receptor beta-gene or a deletion of its germline. The preceding results in nine of 11 patients suggest that abnormal or neoplastic large granular lymphocytes with the characteristics of T and NK cells have an important role in producing the angiocentric/angiodestructive features and lobular panniculitis. Clinically, all three patients with AIL-II and four with AIL-III showed liver dysfunction, cytopenia, and abnormal coagulopathy during the clinical course. Five patients with AIL-III died within 8 months. The histological grading of AIL, patients' age, and limited clinical stage of the disease seem to correlate with response to the treatment and prognosis.

Two cases of myocardial infarction in type 4 Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome is an inherited connective tissue disorder. Clinical manifestations of this syndrome are due to fragile connective tissue. Though many cardiovascular disorders in association with it have been reported, myocardial infarction is quite rare. In this report, two cases with type 4 Ehlers-Danlos syndrome and myocardial infarction are described. Patient 1 was a 30-year-old woman. She was diagnosed as having myocardial infarction on the basis of typical changes in electrocardiograms and serum enzymes (CPK, SGOT and LDH). The diagnosis of type 4 Ehlers-Danlos syndrome was made by the microscopic examination of her connective tissue. Patient 2 was a 32-year-old man. He was also diagnosed as having acute myocardial infarction. His fibroblasts were cultured and they could not synthesize type 3 collagen. Type 4 Ehlers-Danlos syndrome was diagnosed. It was likely that myocardial infarction might have resulted from the fragility of their coronary arteries in type 4 Ehlers-Danlos syndrome.

New formulation of chemical peeling agent: histological evaluation in sun-damaged skin model in hairless mice.

BACKGROUND: chemical peelings injure the superficial skin, which is then restored by healing of the wound. OBJECTIVES: to document the acute and chronic histological changes produced by applying chemical peeling agents used clinically to the UVB-irradiated skin of hairless mice, which served as a model of sun-damaged skin. DESIGN: three chemical peeling agents, 30% salicylic acid, dissolved in macrogol (a new formulation), 35% trichloroacetic acid (TCA) dissolved in distilled water and 20% glycolic acid dissolved in glycerin were applied to the backs of UVB-irradiated hairless mice. Untreated, irradiated areas of skin served as controls. Specimens were evaluated histologically at 3, 14, 28, and 70 days. RESULTS: chronic UVB irradiation produced an irregular hypertrophy of the epidermis. The treated areas of irradiated skin recovered by day 70. At 28 days, all skin specimens treated with chemical peeling agents exhibited a unique connective tissue layer composed of fine collagen fibers beneath the epidermis. While 35% TCA produced severe tissue damage marked by inflammation up to day 14, no inflammatory infiltrates were seen with 30% salicylic acid in macrogol at 70 days. CONCLUSIONS: chemical peeling with 30% salicylic acid dissolved in macrogol led to reorganization of the epidermis and a rebuilding of the superficial dermal connective tissue important in reducing wrinkles, and without evidence of inflammatory infiltrates in an animal model of sun-damaged skin. Findings suggest a possible clinical benefit.

Ultraviolet-B irradiation deforms the configuration of elastic fibers during the induction of actinic elastosis in rats.

We used scanning electron microscopy combined with perfusion fixation, resin injection and a selective digestion procedure to determine the effects of ultraviolet-B (UVB) radiation on the three-dimensional architecture of elastic fibers of rat skin. Chronic irradiation with a suberythematous dose of UVB (3 times/week for 12 weeks) produced a tortuous deformation of the superficial elastic fibers in the skin of the rat sole which normally are linearly arranged. Using computer analysis, we evaluated 40 individuals elastic fibers every 3 weeks for 12 weeks following the irradiation. This procedure confirmed the increasing tortuosity of the fibers, which was related to a decline in the elastic property of the skin in situ. Fine elastic branches developed among the deformed fibers and eventually anastomosed to produce an irregular network in the superficial dermal connective tissue, which may correspond to the development of actinic elastosis, that is, the UV-related accumulation of elastic fiber material.

Reduced amount of secretory component of IgA secretion in tears of patients with atopic dermatitis.

Coupled with the previous finding that sIgA excretion was reduced onto the surface of the skin, we demonstrated that sIgA secretion in the tears of patients with atopic dermatitis (AD) was significantly lower than that of normal subjects, using a small stick made of nitrocellulose membrane. In the bacterial cultures, we have also detected a higher frequency of Staphylococcus aureus in the tears from patients with AD compared to normal subjects. These findings suggested reduced sIgA secretion on the mucous membrane might play a crucial role in the pathomechanisms of the ocular lesions, such as abnormal bacterial flora and ocular complications as well as the establishment of skin lesions in AD.

The proliferative properties of tumor cells differentially correlate with the host immune responses in anogenital Bowen's disease.

Bowen's disease is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. In order to evaluate the relationship between the cytological properties of the tumor cells and the host immune response, we have examined the expression of p53 and proliferating cell nuclear antigen (PCNA), and the number of mitotic cells, clumping cells, koilocytes, Langerhans cells (LCs) and dermal lymphoid cell infiltration in 18 cases of anogenital Bowen's disease. When compared with normal anogenital skins (n = 10), a statistically significant number of p53-positive cells, PCNA-positive cells, mitotic cells, clumping cells, koilocytes and dermal lymphoid cells was observed in the cases of Bowen's disease. Importantly, there existed a very strong correlation between the number of PCNA-positive tumor cells and the number of infiltrated dermal lymphoid cells. Moreover, the number of mitotic cells significantly correlated with the number of intratumoral LCs. The in situ hybridization technique for human papilloma virus (HPV) demonstrated that the HPV-infected Bowen's disease showed a similar histological and immunohistological pattern as the HPV-non-infected counterparts, except for increased koilocyte formation and decreased p53 positivity. The present data suggest that the proliferative activity of Bowen's disease significantly correlates with the host immune reaction, and that the host immune system may differentially recognize the different cytological properties of tumor cells in the Bowen's disease.

Spindle cell hemangioendothelioma exhibits the ultrastructural features of reactive vascular proliferation rather than of angiosarcoma.

A patient with spindle cell hemangioendotheliomas was followed from 1964 to the present time, allowing the authors the opportunity to examine the lesions in the early, mature, and old phases. Organizing thrombi of different stages associated with slit-like vascular proliferation were always observed, whereas cavernous vascular spaces predominated as the lesions became older. Each spindle cell hemangioendothelioma initially developed relatively rapidly and was sometimes painful but then persisted as a silent nodule for decades. Transmission and scanning electron microscopic studies revealed that endothelial cells tended to digitate into the slit-like proliferating channels, became attached to other cells by means of tight junctions, and thus obstructed the channels at sites where thrombi developed repeatedly. The vascular spaces, ranging in nature from slit-like to cavernous, were outlined further by a relatively sparse mantle of ramified or dendritic interstitial cells that corresponded to spindle cells. Most of the cells appeared simply to be fibroblasts, but they developed the features of pericytes when they were close to the endothelial lining of well-developed vascular lumens. Large vascular spaces and phleboliths were surrounded by smooth muscle cells. Approximately 20% of the interstitial cells were dendritic macrophages characterized by phagocytic activity, presence of many lysosomes, and Factor XIIIa expression. The long and characteristic clinical course, the histologic evidence that thrombosis and its organization was continually occurring within the lesions, and the ultrastructural finding that spindle cell hemangioendotheliomas were composed of different microvascular segments from capillaries to veins, suggest that spindle cell hemangioendotheliomas may develop from a cycle of recanalization after thrombosis that occurs repeatedly because of the unique endothelial growth that was noted. This is in contrast with the previous conception that they were low-grade angiosarcomas.

Normal-mode ruby laser for treating congenital nevi.

BACKGROUND: Q-switched laser therapy is known to be highly effective in treating dermal melanocytosis and pigmented epidermal lesions. However, to our knowledge, there are no reports on the effectiveness of laser therapy for congenital nevi. We evaluated the clinical efficacy and side effects of normal-mode ruby laser therapy for congenital pigmented lesions containing abundant melanin. OBSERVATIONS: A normal-mode ruby laser (pulse duration, 0.3-1.0 x 10(-3) seconds; energy fluence, 10-30 J/cm2; and spot size, 10 x 10 or 15 x 15 mm) (Toshiba Corp, Tokyo, Japan) was used to treat 3 patients with congenital nevi at intervals of 1 to 4 months. In all 3 cases, the pigmented lesions were significantly reduced almost to the level of the surrounding normal skin after 4 laser treatments. The treated areas were virtually free of scarring, and the skin texture resembled that of the surrounding normal skin. Unsightly hair growth was also reduced. CONCLUSIONS: The normal-mode ruby laser was effective in treating congenital nevi and produced good cosmetic results. The risk of recurrence is unknown, but the 3 patients in our study did not have any recurrences during the 18- to 39-month study period.

Long- and short-term histological observations of congenital nevi treated with the normal-mode ruby laser.

OBJECTIVE: To evaluate histologically the long- and short-term changes associated with cosmetic improvement or failure of normal-mode ruby laser treatment of patients with congenital nevi. DESIGN: A biopsy of the laser-treated lesions of 10 patients with good or poor cosmetic results was performed at periods up to 8 years 10 months after treatment (mean, 4 years 9 months). Short-term findings were evaluated in 3 patients. SETTING: Ueda Setsuko Clinic and the Dermatology Unit of the Kyushu University, Fukuoka, Japan. PATIENTS: Of the 85 Japanese patients with relatively large congenital nevi who had been treated with the normal-mode ruby laser since 1990, 13 gave informed consent for biopsy and histological examination of the treated area. RESULTS: A long-term follow-up study of the 8 patients with good cosmetic results showed the presence of residual nevus cells 1.11 +/- 0.35 mm (mean +/- SD) (range, 0.63-2.05 mm) below the skin surface. Above these cells was a layer of connective tissue that formed a subtle microscopic scar that preserved the normal structure of the papillary dermis. Hair follicles were damaged at the base, and the hairs were attenuated. However, in the 2 patients with poor cosmetic results, nests of pigmented cells were commonly seen in the epidermis, and melanin was relatively abundant in basal keratinocytes. No malignant changes were observed in any patient. A short-term study in 3 patients showed damage to pigmented cells in the epidermis and upper dermis as observed following electrodesiccation. CONCLUSIONS: Multiple treatments with the normal-mode ruby laser produced immediate thermal damage to the superficial nests of nevus cells and a subsequent remodeling of the superficial connective tissue. When the thickness of the subtle microscopic scar reached 1 mm, it masked the underlying residual nevus cells and achieved a good cosmetic result. Follow-up for at least 8 years after laser treatment showed no evidence of malignant change in the treated areas.

Histologic changes in the skin of hairless mice following peeling with salicylic acid.

OBJECTIVE: To clarify the histologic alterations produced by the application of salicylic acid solution, which has been used effectively in chemical peeling without producing a wound or inflammation. DESIGN: We applied 7.5%, 15.0%, and 30.0% salicylic acid in solutions of ethanol or macrogol to the backs of hairless mice for 20 minutes. The skin was histologically evaluated immediately and at 1, 3, 12, 24, and 48 hours following treatment. SETTING: The Department of Dermatology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. MAIN OUTCOME MEASURES: A loss of cornified cells was the only morphologic alteration associated with the treatment, and was followed by the activation of the epidermal basal cells and the underlying fibroblasts. RESULTS: The 7.5% and 15. 0% salicylic acid solutions produced few histologic changes, whereas the 30.0% salicylic acid in both vehicles macerated and then exfoliated the cornified cells. As the epidermis became thinner, the residual epidermal cells became flattened and were rearranged parallel to the tensile surface load. The cornified material within the hair follicles also became macerated, dilated the follicles, and then dropped off. An apparent increase occurred in the number of cells in the S phase in the epidermal basal cells in 24 hours, leaving the follicular cells unchanged. As the cornified layer thickened in 48 hours, the epidermal cells below it and the underlying fibroblasts resumed their random pretherapy arrangement. Except for the occasional infiltrate of lymphocytes, no degenerative or inflammatory changes occurred. While similar changes occurred with each vehicle, they were relatively faster with the ethanol preparations. CONCLUSION: The present results suggest that the architecture of the epidermis and the papillary dermis can be regenerated by simply injuring the cornified layer by using topical agents such as salicylic acid that do not cause degeneration or inflammation.

Clinical, immunological and MRI features of myelitis with atopic dermatitis (atopic myelitis).

In order to clarify the characteristic features of myelitis with atopic dermatitis (AD), we compared the clinical, immunological and MRI findings between 14 myelitic patients with AD and 12 myelitic patients without AD. The myelitic patients with AD showed the following distinct features, compared with those without AD. (1) A preferential involvement of the cervical cord, as shown by neurologic as well as MRI examinations (14/14 vs. 5/12; P=0.0012), (2) paresthesia/dysesthesia as the predominant symptoms and a rare occurrence of definite muscle weakness (0/14 vs. 5/12; P=0.0120) and dysuria (1/14 vs. 8/12; P=0.0029), (3) a lower Expanded Disability Status Scale score (mean, 1.5 vs. 3.5; P=0.0018), (4) normal cerebrospinal fluid (CSF) findings including those for the IgG index and oligoclonal IgG bands and (5) a persistence of neurologic symptoms and MRI lesions during the follow-up periods (mean, 17 months). In addition, both the serum total IgE level and the frequency of specific IgE to Dermatophagoides farinae were significantly higher in the myelitic patients with AD (median IgE=1266 U/ml, specific IgE 14/14) than in those without AD (145 U/ml, P=0.0034 and 8/12, P=0.0331, respectively) and in 40 healthy controls (86 U/ml, P<0.0001 and 12/40, P<0.0001, respectively). Since myelitis with AD has distinct features and atopy to mite antigens appears to be the underlying cause of this condition, it may therefore be a distinct subtype of myelitis.

Increased number of IgE positive Langerhans cells in the conjunctiva of patients with atopic dermatitis.

AIM: To determine the role of Langerhans cells (LCs) found to bear IgE in patients with atopic dermatitis (AD) by evaluating the surface distribution of these cells in the conjunctival epithelium and epidermis of skin lesions in patients with AD. METHODS: The double labelling method was used to evaluate IgE positive cells that were positive for anti-CD1a or anti-CD23 antibody in an epithelial sheet of the conjunctival limbus. Specimens of conjunctiva were obtained from 12 men, six of whom had AD and ocular complications. Five patients without atopic disease served as controls, plus one additional patient with asthma but no AD. A similar study was conducted using epidermal sheets obtained from two patients with AD and from one without AD. RESULTS: The number of CD1a+ cells present in the conjunctival epithelium of the patients with AD significantly exceeded that of the patients without AD. Most CD1a+ cells in the conjunctival epithelium and epidermis from the patients with AD bore IgE on their surfaces. Few such cells from patients without AD bore IgE. No CD23+ cells were found in the patients with or without AD. CONCLUSIONS: The presence of an increased number of LCs bearing IgE on their surfaces in the conjunctival epithelium of patients with AD suggests that these cells may be involved in eliciting the hypersensitivity reaction and participate in ocular inflammation.

Epidermolysis bullosa herpetiformis (Dowling-Meara type) exhibits ultrastructural derangement of tonofilaments and desmosomes.

Ultrastructural and immunohistochemical studies of clinically intact skin obtained from three severe neonatal cases of epidermolysis bullosa herpetiformis (Dowling-Meara type) demonstrated disorders in the assembly of keratin intermediate filaments and desmosomes of the keratinocytes. During mitosis, K5- and K14-positive and K1- and K10-negative tonofilaments were disrupted and formed spherical bodies associated with intracytoplasmic desmosomes by invagination of the desmosomes and the adjacent plasma membrane. During the invagination process, destructive changes in the internalized membrane were noted. These were accompanied by gradual loss of reactivity with a monoclonal antibody ZK31, which detected plasma membrane adjacent to the attachment plaques of desmosomes. However, the reactivity of the attachment plaques of the internalized desmosomes for desmoplakins and desmoglein did not decline during the process of internalization. In the suprabasal layers of the epidermis, filamentous substructures and K1 and K10 appeared at the periphery of the spherical bodies. Simultaneously, the desmosomes that were sparsely located in the lower epidermis, increased in number as cell differentiation progressed. Thus, the keratinocytes attained an almost normal appearance with respect to tonofilaments and desmosomes by the time they reached the upper layer of the epidermis. These findings may be relevant to the mechanism responsible for the clinical appearance of the herpetiform blisters in epidermolysis bullosa herpetiformis, which are also characterized by spontaneous involution during childhood or when exposed to high ambient temperatures.