Hirschsprung disease (HSCR) is sometimes associated with a set of characteristics including mental retardation, microcephaly, and distinct facial features, but the gene mutated in this condition has not yet been identified. Here we report that mutations in SIP1, encoding Smad interacting protein-1, cause disease in a series of cases. SIP1 is located in the deleted segment at 2q22 from a patient with a de novo t(2;13)(q22;q22) translocation. SIP1 seems to have crucial roles in normal embryonic neural and neural crest development.

Presence of Foxp3+CD25+CD4(+) Treg in the allograft is necessary for allograft survival. GITRL-dependent expansion of Treg within the cornea is one mechanism underlying immune privilege in corneal allografts.

We report a case of a 71-year-old man infected at a nursing home who developed a bullous pemphigoid-like eruption with nail involvement. He was diagnosed by his family doctor as suffering from eczema and was treated with topical corticosteroids, then blisters started appearing. He was next diagnosed as suffering from bullous pemphigoid and treated with oral prednisolone, which worsened his condition. He was finally diagnosed as having crusted scabies with bullous pemphigoid-like eruptions and nail involvement at our clinic. He was then prescribed oral ivermectin (two doses of 12 mg ivermectin with a 1-week interval) and topical lindane (1%gamma-BHC in petrolatum) for scabies with 5% salicylic acid in plastibase as an additional treatment for the crusted lesions on his soles. He showed remarkable improvement in 2 weeks, and his nails showed complete recovery after 7 weeks of occlusive dressing treatment with 1%gamma-BHC. One and a half years later, the patient showed no sign of a recurrence of scabies. The histology of a blister taken from this patient was similar to that of bullous pemphigoid. Direct immunofluorescence showed immunoglobulin (Ig)G and C3 deposition at the dermoepidermal junction similar to that of bullous pemphigoid, but indirect immunofluorescence was negative. The bullous symptoms of this patient were considered to be due to the scabies, because the patient recovered completely after receiving treatment for scabies. Indirect immunofluorescent study is important to distinguish between scabies with blister formation and true bullous pemphigoid.

The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.

Many patients with severe atopic dermatitis (AD) in Japan are afflicted with persistent erythema of the face (atopic red face) that is not only resistant to topical corticosteroid, but often becomes worse with its use. During a three-year period (1991-1993), we treated 79 inpatients with severe AD by a combination of careful daily skin care, use of emollients, and exclusion of exacerbating factors. Occular complications before and after treatment were examined in these cases. After withdrawal of topical corticosteroid, almost all of the patients showed a temporary worsening of their skin condition. Immediately thereafter, their occular symptoms did not change. Cataract was found in 20 cases (25.3%), and retinal detachment in 9 (11.4%). After 2 months, 11 cases of cataract and 5 cases of retinal detachment in the peripheral retina were observed. However, these incidences were similar to the numbers reported in Japan during conventional treatment with topical corticosteroid. The development of cataract or retinal detachment had no relationship to serum IgE levels, personal history of respiratory atopy, the duration of topical corticosteroid use on the face, or treatment with systemic corticosteroid. Our observations suggest that patients who habitually tap or rub their faces strongly tend to develop cataract or retinal detachment at a statistically significant higher frequency. Patients with AD should have ophthalmologic examinations every one to two months for at least one year after a facial oozing attack or withdrawal of corticosteroid.