Faculty Bibliography

Ocular pigmentation in the mouse occurs primarily postnatally as a result of the melanization of neural crest-derived melanocytes. Using immunologic and biochemical techniques, we demonstrate that in normal mice the expression of tyrosinase and the related proteins TRP-1 and TRP-2, rises during the first week of life, remains elevated for a week, and then steadily declines to low levels by adulthood. Sucrose gradient density centrifugation demonstrates that tyrosinase, TRP-1 and TRP-2 are present in high molecular weight forms in the eyes of wild-type mice. The normal time course is disrupted in mice carrying the pink-eyed unstable (p(un)) mutation at the P-locus, a model for tyrosinase-positive albinism in man. Tyrosinase and TRP-2 are present at wild-type levels in the eyes of p(un)/p(un) mice at birth, but, rather than rising, their levels rapidly decline over the first week of life. TRP-1 is almost undetectable, even at birth. High molecular weight complexes could not be detected in eyes of p(un)/p(un) mice. Our results suggest that postnatal ocular melanogenesis in the mouse presents an attractive model for the study of the orderly expression and action of the proteins involved in eumelanin synthesis, and that the p(un) mutation disrupts this temporally controlled process

We cared for an infant girl with the clinical constellation of supraumbilical midabdominal raphe, sternal atresia, and cutaneous facial and upper trunk hemangioma. This is the first report of this clinical association in the dermatologic literature. The vascular component of the disorder responded to flashlamp-pumped pulsed dye laser therapy and to systemic interferon alfa-2a (Roferon-A)

OBJECTIVE. Varicella-zoster virus (VZV) infections can cause severe disease in immunocompromised individuals. To evaluate the spectrum of VZV infections in human immunodeficiency virus (HIV)-infected children, we retrospectively analyzed all the cases of VZV infection in a cohort of children cared for at a hospital for infectious diseases in Bucharest, Romania. METHODS. The records of 391 HIV-infected children admitted to the acquired immunodeficiency syndrome pavilion of Colentina Hospital during the period January 1, 1991, through March 31, 1992, were reviewed for evidence of VZV infection. The diagnosis of varicella or zoster was made clinically and information was collected concerning course of the illness, number of skin lesions, and clinical evidence of complications. Lymphocyte subpopulation typing, as an estimate of immune function, was performed by either a standard fluorescent activated flow cytometric method or by immunofluorescent technique. RESULTS. Thirty-eight cases of varicella (9.7%) and seven cases of zoster (1.8%) were adequately documented among the 391 records reviewed. The duration of varicella was prolonged; in 57% of the children it was greater than 10 days. Forty percent of children with varicella developed a complication, including superinfection of the skin, pneumonia, or thrombocytopenia. None of the children developed clinical hepatitis or encephalitis. Two children (5%) died during varicella, both of respiratory failure. None of the 7 children with zoster had chronic, recurrent, or disseminated lesions. Lymphocyte subset analysis was available for 22 of 38 children with varicella and 3 of 7 children with zoster. Fifteen of the 22 children had normal, age-adjusted, absolute CD4 counts within 3 months of the diagnosis of varicella. All 3 children with zoster who had lymphocyte subset analysis had low CD4 counts and absolute numbers. None of the 45 children received antiretroviral therapy and only 1 child with varicella and 1 with zoster received acyclovir. CONCLUSIONS. The spectrum of VZV infection in this hospitalized group of HIV-infected children was broad. The majority (57%) experienced a prolonged course of disease and a higher rate of complications than normal children hospitalized with varicella

BACKGROUND: Kaposi's sarcoma (KS) is commonly associated with the acquired immunodeficiency syndrome (AIDS) in adults. Little is known regarding its occurrence in children. OBJECTIVE: Our purpose was to report the clinical and epidemiologic characteristics of KS in three Romanian children with AIDS and to compare them with previously reported AIDS-associated KS in children. METHODS: This was a clinicopathologic study and computer-based literature review. RESULTS: All three Romanian children had skin involvement; two had involvement of lymph nodes and internal organs. All had acquired human immunodeficiency virus (HIV) infection postnatally. Including these children, 33 cases of AIDS-associated KS in children have been reported. Thirteen of 30 evaluable patients had acquired HIV infection postnatally; nine of these children (69%) had cutaneous involvement by KS. A perinatal route of transmission was present in the remaining 17 cases; only two of these children (12%) with KS had cutaneous involvement. No case was noted in which intravenous drug use was the sole parental HIV risk factor. CONCLUSION: The data support the contention that KS is caused by a second infectious agent prevalent only in certain HIV-infected populations. Children of parents in high-risk groups for KS and children who acquire HIV via contaminated blood or blood products are at highest risk for KS. The route of acquisition of HIV infection may also be associated with different clinical manifestations of KS in children

Coated vesicles play a critical role in the process of melanogenesis. Antisera raised against a coated vesicle fraction from mouse melanoma cells recognize two major glycoprotein antigens, band I (47-55 kd) and band II (90-120 kd). We demonstrate that band II is lysosome-associated membrane protein 1 (LAMP-1) by the following criteria: 1) the molecular weight and abundance of LAMP-1 varies among tissues but is always identical to that of band II; 2) band II and LAMP-1 co-migrate in sucrose gradient sedimentation studies; 3) immunodepletion of cell extracts with antivesicle serum removes all LAMP-1; and 4) intact organelles immunoisolated with antivesicle serum contain band II and LAMP-1. Our results further confirm the long-suspected relationship between melanosomes and the lysosomal lineage of organelles

Are tyrosinase, encoded at the albino locus, and tyrosinase-related protein-1 (TRP-1), encoded at the brown locus, similarly distributed in melanocytes? We determined the subcellular distribution of tyrosinase and TRP-1 using density fractionation of postnuclear supernatants from mouse melanoma cells of defined genotype followed by immunoblotting with specific antipeptide sera. In highly melanized cells, the majority of tyrosinase cosedimented on Percoll density gradients with visible melanin and with the peak of DOPA incorporation, confirming its presence predominantly in stage III-IV melanosomes. In contrast, the distribution of TRP-1 was limited to a less-dense melanosomal compartment, devoid of melanin. In amelanotic or minimally melanized cells, the majority of tyrosinase shifted into these lighter peaks. To explore a suspected relationship between lysosomes and melanosomes, we analyzed the distribution of lysosome-associated membrane protein-1 (LAMP-1). An overlap in the distribution of LAMP-1 and TRP-1 was demonstrated by immunomicroscopy and confirmed by immunoisolation. LAMP-1 was not present in the dense, melanin-rich melanosomal peak on gradient analysis. TRP-1 from melanoma cells homozygous for the brown mutation is not fully glycosylated, is more rapidly degraded, and is restricted in its distribution compared to its wild-type counterpart. In these mutant cells, all melanosomal compartments contain LAMP-1. Our results demonstrate that in wild-type cells the majority of tyrosinase eventually localizes to stage III-IV melanosomes. TRP-1 is limited to a less dense melanosomal compartment that is also LAMP-1 positive. The existence of this compartment suggests that it may represent a common step in the biogenesis of melanosomes and lysosomes