Outcomes after reperfusion therapies in patients with ACA stroke: A multicenter cohort study from the EVATRISP collaboration.

BACKGROUND: Patients with stroke secondary to occlusions of the anterior cerebral artery (ACA) often have poor outcomes. The optimal acute therapeutic intervention for these patients remains unknown. METHODS: Patients with isolated ACA-stroke were identified from 10 centers participating in the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) prospective registry. Patients treated with endovascular thrombectomy (EVT) were compared to those treated with intravenous thrombolysis (IVT). Odds ratios with 95% confidence intervals (OR; 95%CI) were calculated using multivariate regression analysis. RESULTS: Included were 92 patients with ACA-stroke. Of the 92 ACA patients, 55 (60%) were treated with IVT only and 37 (40%) with EVT (±bridging IVT). ACA patients treated with EVT had more often wake-up stroke (24% vs. 6%, p = 0.044) and proximal ACA occlusions (43% vs. 24%, p = 0.047) and tended to have higher stroke severity on admission [NIHSS: 10.0 vs 7.0, p = 0.054). However, odds for favorable outcome, mortality or symptomatic intracranial hemorrhage did not differ significantly between both groups. Exploration of the effect of clot location inside the ACA showed that in patients with A1 or A2/A3 ACA occlusions the chances of favorable outcome were not influenced by treatment allocation to IVT or EVT. DISCUSSION: Treatment with either IVT or EVT could be safe with similar effect in patients with ACA-strokes and these effects may be independent of clot location within the occluded ACA.

Task-Specific Motor Rehabilitation Therapy After Stroke Improves Performance in a Different Motor Task: Translational Evidence.

While the stroke survivor with a motor deficit strives for recovery of all aspects of daily life movements, neurorehabilitation training is often task specific and does not generalize to movements other than the ones trained. In rodent models of post-stroke recovery, this problem is poorly investigated as the training task is often the same as the one that measures motor function. The present study investigated whether motor training by pellet reaching translates into enhancement of different motor functions in rats after stroke. Adult rats were subjected to 60-min middle cerebral artery occlusion (MCAO). Five days after stroke, animals received either training consisting of 7 days of pellet reaching with the affected forelimb (n = 18) or no training (n = 18). Sensorimotor deficits were assessed using the sticky tape test and a composite neuroscore. Infarct volumes were measured by T2-weighted MRI on day 28. Both groups of rats showed similar lesion volume and forelimb impairment after stroke. Trained animals improved in the sticky tape test after day 7 post-stroke reaching peak performance on day 14. More reaching attempts during rehabilitation were associated with a better performance in the sticky tape removal time. Task-oriented motor training generalizes to other motor functions after experimental stroke. Training intensity correlates with recovery.

Stimulation of cellular sphingomyelin import by the chemokine connective tissue-activating peptide III.

The selective import of phospholipids into cells could be mediated by proteins secreted from the cells into the extracellular compartment. We observed that the supernatants obtained from suspensions of thrombin-activated platelets stimulated the exchange of pyrene (py)-labeled sphingomyelin between lipid vesicles in vitro. The proteins with sphingomyelin transfer activity were purified and identified as the chemokine connective tissue-activating peptide III (CTAP-III) and platelet basic protein. Isolated CTAP-III stimulated the exchange of py-sphingomyelin between lipid vesicles but did not affect the translocations of py-labeled phosphatidylcholine and phosphatidylethanolamine. CTAP-III rapidly increased the transfer of py-sphingomyelin from low density lipoproteins into peripheral blood lymphocytes, other immune cells, and fibroblasts. In the presence of heparin, CTAP-III was unable to insert sphingomyelin into the peripheral blood lymphocytes. The activation energy of the py-sphingomyelin transfer suggested that the translocation proceeded entirely in a hydrophobic environment. [(3)H]Sphingomyelin transferred to the cells by CTAP-III was hydrolyzed to [(3)H]ceramide and [(3)H]sphingosine after activation with tumor necrosis factor alpha. The generation of the [(3)H]sphingolipid messengers was catalyzed by acid sphingomyelinase. Our results identify CTAP-III as the first mediator of the selective (endocytosis-independent) cellular import of sphingomyelin allowing the paracrine modulation of the sphingolipid signaling.

Serum IgG, IgM, and IgA reactivity to human papillomavirus types 11 and 6 virus-like particles in different gynecologic patient groups.

Serum samples from several groups of patients attending a gynecology clinic were analyzed by ELISA for specific antibodies recognizing surface epitopes on intact human papillomavirus (HPV) types 6 and 11 L1 virus-like particles (VLPs) that were synthesized in vitro. In these samples, positive IgG and IgM reactivities to HPV-11 L1 VLPs were, respectively, 12% and 6% for 87 controls, 46% and 67% for 79 condyloma patients, 30% and 64% for 72 cervical intraepithelial neoplasia patients, 16% and 19% for 63 pregnant women at time of delivery, and 5% and 0 in their 63 newborns. IgA reactivities were low and not significantly different. The prevalence of IgG-positivity in HPV-6/11 DNA-positive patients increased from 46% with HPV-11 L1 VLPs to 76% when the sera were additionally screened with HPV-6 L1 VLPs. These data show that HPV-6 and -11 L1 VLPs are effective antigens for serologic studies and they detect type-specific antibodies.

Pride and mastery in children with autism.

The goal of this study was to compare expressions of pride and mastery in samples of preschool autistic, mentally retarded and normal children. A paradigm was used in which children completed developmentally appropriate puzzles, both with and without praise. Results indicated that compared to the other children, as many autistic children smiled upon completion of the task, but many fewer looked up to share their pleasure with the parent or experimenter or drew attention to the task. Moreover, significantly more autistic children showed avoidant responses, particularly in response to praise. These findings are discussed in terms of theoretical issues regarding the development of pride and mastery in children with significant social deficiencies.

Clinical trial of natural human lymphocyte-derived interleukin 2 in cancer patients: effects on cytokine production and suppressor cell status.

Lymphocyte-derived, natural, glycosylated interleukin 2 (IL 2) may have different effects in vivo than the non-glycosylated recombinant IL 2 hitherto employed in clinical trials. To test this, 9 tumor patients were given 3-6 x 10(6) U/day natural IL 2 by continuous infusion for 5 days. Compared with previously published results obtained using recombinant IL 2, as far as similar tests were performed, no unexpected results were obtained with natural IL 2 in the present study. Plasma TNF-alpha levels increased considerably during therapy, IFN-gamma very slightly, whereas IL 2-stimulated secretion of either cytokine in vitro fluctuated greatly. CD16+ and CD25+ cells increased and CD45R+ cells decreased after treatment, consistent with significant lymphocyte activation in vivo. MHC-unrestricted cytotoxicity increased after treatment. The level of CD8+ cells was and remained within the normal range, although suppressive activity generated in mixed lymphocyte culture was deficient prior to therapy. Interestingly, this normalised after therapy. These results extend studies of immunological monitoring of patients receiving IL 2, based on the first trial using natural rather than recombinant IL 2.

Cytokine regulation of the balance between alloindifferent and allospecific suppressor induction in mixed lymphocyte cultures.

The effects of exogenous cytokines on the generation of alloindifferent, MHC-unrestricted suppressive activity early on in mixed lymphocyte culture interactions have been investigated. Interleukin 4 strongly blocked the generation of suppression, whereas IL-1, IL-2, and IL-6 enhanced it to some extent. Tumor necrosis factor-alpha, interferons-alpha and -gamma, granulocyte/macrophage colony-stimulating factor, granulocyte CSF, IL-3 and IL-5, and a number of combinations of these factors were without effect in this system. Insofar as the alloindifferent suppression studied here also inhibited the development of allospecific, MHC restricted suppressive activity later in MLC, reduction by IL-4 of its development may have relevance for the use of this cytokine to facilitate the induction of specific suppressor cell-mediated transplantation tolerance in vivo.

Structural organization and sequence of the homeotic gene Antennapedia of Drosophila melanogaster.

The structure of the Drosophila melanogaster Antennapedia (Antp) gene has been investigated by the isolation and sequencing of different cDNAs and genomic clones. Northern analysis, S1 mapping and primer extension experiments reveal a complex and unusual gene structure. The gene is composed of two promoters, eight exons spanning >100 kb, and two termination processing regions. Four major polyadenylated transcripts were found, two of them starting at a second internal promoter in front of exon 3. All four transcripts have extremely long untranslated leader and trailer sequences in the range of 1-2 kb. Despite the complex transcriptional organization, the open reading frame is the same in all transcripts, and starts in exon 5 giving rise to a protein of mol. wt. 42 800. The putative protein is rich in glutamine (18%) and proline (10%). The homeobox, a region which previously has been shown to be highly conserved among homeotic genes, is contained in the open reading frame and located in the last exon. Functional implications of the complex structure with respect to development and its relation to the mutant phenotypes are discussed.

Combined pharmaco-EEG and pharmacopsychological study to estimate CNS effects of ketanserin in hypertensive patients.

When developing a new compound, potential side effects on the central nervous system (CNS) should be systematically investigated to determine the drug's safety, e.g., in respect of operating machinery or driving a car. The present study investigated CNS effects of ketanserin, a newly developed S2-serotonergic antagonist, in hypertensive patients. A multidimensional research strategy was used combining pharmaco-EEG and pharmacopsychological methods. The investigation consisted of two separate double-blind, randomized, and placebo-controlled studies, which were, however, planned together and in part included the same patients. The first study was carried out in 2 X 24 patients receiving chronic treatment with 2 X 20 mg ketanserin for 2 weeks, followed by 2 X 40 mg for a further 3 weeks. The second study was performed in 2 X 20 patients after subacute administration of 20 mg twice daily for six days. A multidimensional research strategy was employed to investigate CNS effects on functional and performance measures. Vigilance-related parameters, such as the alpha slow wave index and the absolute delta power, were assessed with pharmaco electroencephalography. Critical flicker-fusion frequency served as a measure of central sedation. Psychomotor performance and concentration tests were used to detect CNS effects which might impair car-driving ability. In addition, subjective well-being and adverse drug reactions were recorded. Ketanserin proved to be a safe drug to lower blood pressure. Only after chronic treatment were there slight indications that ketanserin could have a sedating and inhibiting action on the CNS. However, the differences between placebo and the ketanserin group, and the alterations within each group, were so minimal that they were not considered clinically relevant. A negative effect of ketanserin on car-driving ability is not very likely. The results show that the model was sensitive enough to detect CNS effects with sufficient certainty.

Cloning of the homeotic Sex combs reduced gene in Drosophila and in situ localization of its transcripts.

We have extended our ;chromosomal walk' in the Antennapedia-complex (ANT-C) by isolating overlapping DNA sequences spanning the chromosomal segment between Antennapedia (Antp) and Deformed (Dfd). The transcription units, homeoboxes and M-repeats were mapped within this region. Four transcription units Antp, fushi tarazu (ftz), Sex combs reduced (Scr) and Dfd contain both a homeobox and an M repeat, whereas at least two additional transcription units, x and z, were found to lack these elements. The Scr locus was identified by deletion mapping. It consists of at least two exonic regions separated by a large intron. The homeobox is located in the 3' exon and is 82% homologous to the one in Antp. Scr encodes a major 3.9-kb RNA. A corresponding cDNA clone was used as a probe for in situ hybridization to sections of various embryonic stages. At gastrula stages Scr transcripts accumulate in the posterior head and the anterior thoracic region of the germ band. At later stages a strong accumulation of transcripts is observed in the suboesophageal and the prothoracic ganglion of the ventral nervous system.