Splenic smooth-muscle tumors in children with acquired immunodeficiency syndrome: report of two cases of this unusual location with evidence of an association with Epstein-Barr virus

Smooth-muscle neoplasms are rarely located in the spleen. They have been previously reported in five cases of children with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS). Two cases of children with HIV infection/AIDS with autopsy and surgical pathology evidence of multiple smooth-muscle neoplasms with splenic involvement are presented. DNA was extracted from histology slides in both cases for analysis for Epstein Barr (EB) virus. In both cases, the presence of EB virus was confirmed. This paper documents two additional cases of the unusual phenomenon of splenic involvement by smooth-muscle neoplasms in the setting of AIDS in childhood and further supports the role of EB virus in the development of these neoplasms. Received: 27 January 1999 / Accepted: 23 August 1999     

Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family

The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family.     

Multiplex polymerase chain reaction.

The polymerase chain reaction (PCR) is a widely utilized assay for specifically amplifying small fragments of DNA. Multiplex PCR is the amplification of more than one DNA fragment per reaction and has many potential uses. When more than one primer set per reaction tube is utilized, the total number of tubes in any one experiment may be reduced, conserving expensive reagents and decreasing possible contamination. Multiplex PCR allows for an assay of the gene of interest and assures that the amplification process proceeds as expected with the use of a companion control genome primer set. Multiplex PCR is useful in assaying DNA extracted from samples of immunocompromised patients in which more than one infectious agent may be suspected such as simultaneous EBV and CMV detection. Multiplex PCR offers many advantages over single reaction PCR and has been found to be an useful adjunct in our laboratory.     

Sleep deprivation effects on growth factor expression in neonatal rats: a potential role for BDNF in the mediation of delta power

The sleeping brain differs from the waking brain in its electrophysiological and molecular properties, including the expression of growth factors and immediate early genes (IEG). Sleep architecture and homeostatic regulation of sleep in neonates is distinct from that of adults. Hence, the present study addressed the question whether the unique homeostatic response to sleep deprivation in neonates is reflected in mRNA expression of the IEG cFos, brain-derived nerve growth factor (BDNF), and basic fibroblast growth factor (FGF2) in the cortex. As sleep deprivation is stressful to developing rats, we also investigated whether the increased levels of corticosterone would affect the expression of growth factors in the hippocampus, known to be sensitive to glucocorticoid levels. At postnatal days 16, 20, and 24, rats were subjected to sleep deprivation, maternal separation without sleep deprivation, sleep deprivation with 2 h recovery sleep, or no intervention. mRNA expression was quantified in the cortex and hippocampus. cFos was increased after sleep deprivation and was similar to control level after 2 h recovery sleep irrespective of age or brain region. BDNF was increased by sleep deprivation in the cortex at P20 and P24 and only at P24 in the hippocampus. FGF2 increased during recovery sleep at all ages in both brain regions. We conclude that cortical BDNF expression reflects the onset of adult sleep-homeostatic response, whereas the profile of expression of both growth factors suggests a trophic effect of mild sleep deprivation.     

Development of enzymatically degradable protective coatings for use in triggered drug delivery systems: derivatized starch hydrogels.

Starch is a common polysaccharide which consists of glucopyranose residues in an alpha-D-(1-4) linkage that yields D-glucose upon hydrolysis. Saturated aqueous solutions of soluble starch are easily reacted in the presence of glycidyl methacrylate to produce methacrylate grafted starch. Grafted starch solutions were polymerized to produce hydrogels, with and without the addition of an unsaturated acid. The grafted starch solutions and the resulting hydrogels are both shown to be degraded by the enzyme alpha-amylase. These acidic hydrogels are potentially useful as enzymatically degradable protective coatings in self-regulated drug delivery system applications. The pH of an acidic starch hydrogel required by this self-regulated drug delivery system does indicate that an adequately acidic hydrogel can be produced.     

The role of complement in the induction of antibody responses.

To determine the effect of complement on the normal antibody response to T cell-dependent antigens, we immunized normal and C4 deficient guinea-pigs with bacteriophage phi X 174. Following primary immunization with a standard dose (2 X 10(9) PFU/Kg) given intravenously. C4 deficient guinea-pigs produced less antibody than normal guinea-pigs and were unable to maintain measurable antibody levels. Following secondary immunization, antigen clearance of C4 deficient guinea-pigs was delayed and the subsequent antibody response was identical to their primary response without amplification or isotype switch. Increased antigen dose and administration of antigen in adjuvants into footpads improved the responses but did not make them normal. The primary and secondary responses became essentially normal, however, when small amounts of normal guinea-pig serum were given to the deficient animals at the time of the primary (but not the secondary) immunization. We postulate that the contribution of complement to the mature humoral immune response is related to activation of C3. Our data show that antigen initiates a primary immune response. The resultant antigen-antibody complexes interact with complement and are then non-specifically trapped by C3 receptors on dendritic cells, B cells and macrophages. Thus, antigen is selectively accumulated within the lymphoid organs and in turn 'captures' antigen specific B cells by interaction of the trapped antigen with antigen specific sIg. The approximation of specific lymphoid cells, macrophages and antigen permits generation of specific memory cells and ensures prompt, mature antibody response on subsequent antigen exposure.