Custom Integrated Circuits

Contains reports on nine research projects.Analog Devices, Inc.International Business Machines, Inc.Joint Services Electronics Program (Contract DAALO03-86-K-0002)U.S. Air Force - Office of Scientific Research (Grant AFOSR 86-0164)Rockwell International CorporationOKI SemiconductorU.S. Navy - Office of Naval Research (Contract N00014-81-K-0742)Charles Stark Draper LaboratoryDARPA/U.S. Navy - Office of Naval Research (Contract N00014-80-C-0622)DARPA/U.S. Navy - Office of Naval Research (Contract N00014-87-K-0825)National Science Foundation (Grant ECS-83-10941)AT&T Bell Laboratorie

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

<p>Abstract</p> <p>Background</p> <p>In <it>Plasmodium falciparum</it>-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.</p> <p>Methods</p> <p>Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay.</p> <p>Results</p> <p>The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.</p> <p>Conclusion</p> <p>The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.</p

Leiomyosarcoma in urinary bladder after cyclophosphamide therapy for retinoblastoma and review of bladder sarcomas

We report an unusual case of a leiomyosarcoma of the urinary bladder after chemotherapy for retinoblastoma and the results of a review of the published reports of bladder sarcomas. A 22-year-old man presented with hematuria and was found to have a mass in his urinary bladder on computed tomography. Transurethral resection of the mass revealed a leiomyosarcoma. The patient underwent radical cystectomy and an ileal conduit was created. The final pathologic examination confirmed high-grade leiomyosarcoma. Prospective randomized combination trials similar to the Intergroup Rhabdomyosarcoma Study in the pediatric population are necessary to better understand and manage these potentially curable sarcomas