Transcranial Doppler sonographic monitoring during cerebral aneurysm embolization: a preliminary report

BACKGROUND AND PURPOSE: The wide application of embolization in the treatment of aneurysms has created the need for an intraprocedural means to anticipate a poor outcome by monitoring hemodynamic changes in the brain. METHODS: Transcranial Doppler sonography was used to monitor flow velocity in the middle cerebral artery (MCA) in 23 patients undergoing embolization with Guglielmi detachable coils (GDCs) of either incidental or symptomatic intracranial aneurysms. Sonographic values were recorded from the ipsilateral MCA at the beginning, middle, and end of the interventional procedure and 24 hours afterward. RESULTS: No complications occurred in 15 patients. In these cases, sonography showed an average decrease in MCA flow velocity of 2.7% after GDC application, returning to baseline at the end of treatment and then increasing by about 17% 24 hours later. In four patients with vasospasm on posttreatment angiograms, MCA flow velocity increased to values higher than 120 cm/s after GDC application, returning to baseline after 24 hours. In four patients with ischemic complications (two transient ischemic attacks, one stroke, one vascular death), MCA flow velocity decreased more than 30% and did not return to preoperative values within 24 hours. CONCLUSION: The application of transcranial Doppler sonographic monitoring during endovascular treatment may help to identify patients at risk for posttreatment cerebral ischemia.     

Malignant hyperthermia during prolonged surgery for tumour resection

Patients with subacute cutaneous lupus erythematosus (SCLE) have circulating antibodies to Ro/SSA directed to two antigenically distinct ribonucleoproteins of 60 kDa and 52 kDa. Three laboratory tests may be used to detect anti-Ro/SSA antibodies: counterimmunoelectrophoresis (CIE), enzyme-linked immunosorbent assay (ELISA) and immunoblotting (IB). Their relative efficacy and clinical correlations were ascertained. We determined anti-Ro/SSA antibodies with CIE, with two different ELISA methods (ELISA 1 and 2) and with IB in 29 SCLE patients. Anti-52 kDa and -60 kDa Ro/SSA antibodies were also assayed with IB. In addition, we determined antinuclear antibodies with indirect immunofluorescence, anti-Sm, anti-RNP, anti-La/SSB and anti-Ro/SSA antibodies with CIE and ELISA, and anti-nDNA and cardiolipin antibodies using an ELISA method. CIE detected anti-Ro/SSA antibodies in 22 patients while ELISA 1 and 2 did so in 17 and 18 patients, respectively. In five patients, IB revealed a reactivity to 60 kDa polypeptides and in two, a reactivity to 52 kDa polypeptides. Of these seven patients, four had a myocardial infarction. Of these, two reacted to the 52 kDa antigen and two to the 60 kDa antigen. A combination of techniques was often needed to detect all specificities. ELISA proved to be very specific and sensitive. The IB technique detected a group of patients with myocardial infarction. A case-control study is needed to confirm the data of cardiac involvement.     

Gene structure, expression pattern, and biological activity of mouse killer cell activating receptor-associated protein (KARAP)/DAP-12

Natural killer cell and T cell subsets express at their cell surface a repertoire of receptors for MHC class I molecules, the natural killer cell receptors (NKRs). NKRs are characterized by the existence of inhibitory and activating isoforms, which are encoded by highly homologous but separate genes present in the same locus. Inhibitory isoforms express an intracytoplasmic immunoreceptor tyrosine-based inhibition motif, whereas activating isoforms lack any immunoreceptor tyrosine-based inhibition motif but harbor a charged amino acid residue in their transmembrane domain. We previously characterized KARAP (killer cell activating receptor-associated protein), a novel disulfide-linked tyrosine-phosphorylated dimer that selectively associates with the activating NKR isoforms. We report here the identification of the mouse KARAP gene, its localization on chromosome 7 and its genomic organization in five exons. Point mutation and transfection studies revealed that KARAP is a novel signaling transmembrane subunit whose transduction function depends on the integrity of an intracytoplasmic immunoreceptor tyrosine-based activation motif. In contrast to previous members of the immunoreceptor tyrosine-based activation motif polypeptide family, KARAP is ubiquitously expressed on hematopoietic and nonhematopoietic cells, suggesting its association with a broad range of activating receptors in a variety of tissues.     

Nup154, a new Drosophila gene essential for male and female gametogenesis is related to the nup155 vertebrate nucleoporin gene

The Nup154 gene of Drosophila encodes a protein showing similarity with known nucleoporins: rat Nup155 and yeast Nup170 and Nup157. Hypomorphic mutant alleles of Nup154 affected female and male fertility, allowing investigation of the gene function in various steps of oogenesis and spermatogenesis. Nup154 was required in testes for cyst formation, control of spermatocyte proliferation and meiotic progression. In ovaries, Nup154 was essential for egg chamber development and oocyte growth. In both the male and female germ line, as well as in several other cell types, the Nup154 protein was detected at the nuclear membrane, but was also present inside the nucleus. Intranuclear localization has not previously been described for rat Nup155 or yeast Nup170 and Nup157. In mutant egg chambers the Nup154 protein accumulated in the cytoplasm, while it was only barely detected at the nuclear envelopes. FG repeats containing nucleoporins detected with mAb414 antibody were also mislocalized to a certain extent in Nup154 mutant alleles. This suggests that Nup154 could be required for localizing other nucleoporins within the nuclear pore complex, as previously demonstrated for the yeast Nup170. On the other hand, no evident defects in lamin localization were observed, indicating that Nup155 mutations did not affect the overall integrity of the nuclear envelope. However, ultrastructural analyses revealed that in mutant cells the morphology of the nuclear envelope was altered near the nuclear pore complexes. Finally, the multiplicity of phenotypes observed in Nup154 mutant alleles suggests that this gene plays a crucial role in cell physiology.     

Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells

IL-10 is a well-documented immunosuppressant that inhibits macrophage-dependent Ag presentation and CD4+ T cell proliferation in vitro. We report that IL-10 inhibits alloantigen-specific proliferative responses and induces a long lasting anergic state in human purified CD8+ T cells when added concomitantly with the Ag in the presence of APC. Moreover, the generation of allospecific cytotoxic activity is inhibited by IL-10. These effects are indirect and are mediated through inhibition of the costimulatory functions of APC. In contrast, IL-10 has no direct inhibitory effects on the proliferation of purified CD8+ T cells activated by anti-CD3 mAb and promotes the growth of activated CD8+ T cells in combination with low doses of IL-2. Taken together, these results indicate that IL-10 has differential effects on CD8+ T cells depending on their state of activation, which may explain both the enhancing and inhibitory effects observed after IL-10 treatment in different in vivo experimental models.