ABSTRACT
Linear IgA bullous dermatosis (LABD) in adults is characterized by subepidermal bullae associated with a linear deposition of IgA at the basement membrane zone. Its cause is unclear, although it appears to have an immune-mediated basis. The development of LABD in a cancer patient undergoing immunotherapy has been described in the French literature. We describe a similar case of LABD arising in a patient while undergoing interleukin-2 immunotherapy for renal cell carcinoma.
Subject(s)
Immunoglobulin A , Interleukin-2/adverse effects , Skin Diseases, Vesiculobullous/chemically induced , Aged , Humans , Immunoglobulin A/metabolism , Male , Skin Diseases, Vesiculobullous/metabolismABSTRACT
Twelve transgenic founder animals retaining intact copies of the infectious molecular clone of human immunodeficiency virus (HIV)-1 were obtained. All the founders appeared healthy during a 9- to 12-month observation period. However, transgenic offspring of one of the founders (female #13), died within the 1st month of life while manifesting several symptoms characteristic of human AIDS. To discover why only one transgenic lineage was affected and why the founder animal in the affected lineage remained healthy while all of her transgenic offspring were diseased, we compared the organization of the transgene in the transgenic lineages. Restriction enzyme analysis showed that the founder no. 13 was a mosaic carrying in each transgenic cell four tandemly arranged copies of the infectious molecular clone. All the units of the tandem repeat appeared to be correctly preserved with the exception of the 3'-most copy, which terminated near the start of human sequences that flank the 3' long terminal repeat (LTR). The unaffected founders and their transgenic litter usually carried a high number of copies of the provirus. The 5' terminus of the transgene in the unaffected animals appeared to be deleted or rearranged. None of the 12 transgenic founders carried a single copy of integrated provirus. We conclude that infectious molecular clone of HIV-1 can be expressed in transgenic mice, and that the mode of proviral integration similar to that seen during the retroviral infectious cycle (i.e., a single-copy provirus) may be incompatible with the postnatal survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Genes, Viral , HIV-1/genetics , Proviruses/genetics , Animals , Cloning, Molecular , Female , Gene Expression , Male , Mice , Mice, TransgenicABSTRACT
Transgenic mice containing intact copies of the human immunodeficiency virus (HIV) proviral DNA were constructed. Founder animals were not viremic for HIV and remained healthy during a 9-month observation period. After being mated with nontransgenic animals, one founder mouse (No. 13) gave rise to F1 progeny that developed a disease syndrome characterized by marked epidermal hyperplasia, lymphadenopathy, splenomegaly, pulmonary lymphoid infiltrates, growth retardation, and death by day 25 of life. Infectious HIV, indistinguishable from parental virus by immunoblot analysis, was recovered from the spleen, lymph nodes, and skin of five of five affected animals.
