Disseminated adenovirus infection in two premature infants.

We present two premature infants with disseminated neonatal adenovirus infection, whose epidemiology, clinical course and outcome differ to a great extent. The first infant, born vaginally at 35 weeks gestational age after premature rupture of membranes and maternal illness, developed pneumonia, hepatitis and coagulopathy and died of circulatory failure at the age of 17 days. The other infant, delivered by cesarean section at 36 weeks gestational age, did - in contrast to all documented cases in the literature - not show any signs of pneumonia and survived meningitis without sequelae. The mode of transmission of the viral infection may have been via the maternal birth canal in the first infant and transplacental in the second one. Diagnosis was obtained by direct immunofluorescent test and serology in the first patient and by maternal serology and the detection of viral antigen in tracheal aspirates (ELISA) in the second patient. Disseminated neonatal adenovirus infection has a high mortality and should be considered in the differential diagnosis of neonatal sepsis, especially when pneumonia, hepatitis and neurologic symptoms develop together with thrombocytopenia or disseminated intravascular coagulopathy.

Biosynthetic labeling of beta-hexosaminidase B: inhibition of the cellular uptake of lysosomal secretions containing [3H]hexosaminidase B by insulin-like growth factor-II in rat C6 glial cells.

The insulin-like growth factor-II/mannose-6-phosphate receptor binds two classes of ligands, IGF-II and lysosomal enzymes containing the mannose-6-phosphate recognition marker. To study the interaction of the two classes of ligands at the receptor level, we have isolated 'high uptake' forms of lysosomal enzymes containing mannose-6-phosphate that had been radiolabeled biosynthetically using a tissue culture model: Tay-Sachs disease fibroblasts were incubated in medium containing [3H]mannose, ammonium chloride and mannose-6-phosphate. Under the conditions of these experiments, the Tay-Sachs disease fibroblasts synthesized and secreted radiolabeled hexosaminidase B, as confirmed by measuring enzymatic activity of cell-conditioned medium. The enzyme secreted was recognized by antibodies raised against purified hexosaminidase A and B but not by nonimmune control sera in Western blotting and immunoprecipitation experiments. The radiolabeled cell-conditioned medium was partially purified by ion-exchange chromatography on a DEAE-Sephadex column. When partially purified [3H]hexosaminidase B was incubated with rat C6 glial cells which express large numbers of IGF-II/mannose-6-phosphate receptors, the enzyme was taken up specifically via the IGF-II/mannose-6-phosphate receptor as evidenced by carbohydrate competition experiments. The specific uptake of the radiolabeled lysosomal enzyme was partially inhibited by IGF-II and an antibody against the IGF-II/mannose-6-phosphate receptor (No. 3637). We conclude that the cellular uptake of a biosynthetically labeled lysosomal enzyme, hexosaminidase B, is partially inhibited by IGF-II. We hypothesize that IGF-II might be capable of modulating lysosomal pathways in vivo.