Glucose attenuation of atropine-induced deficits in paradoxical sleep and memory

When administered systemically, glucose attenuates deficits in memory produced by several classes of drugs, including cholinergic antagonists and opiate agonists. Glucose also enhances memory in aged rats, mice, and humans. In addition, glucose ameliorates age-related reductions in paradoxical sleep. Because deficits in paradoxical sleep are most marked in those individual aged rats that also have deficits in memory, treatments which improve one of these functions may similarly improve the other. The present experiments show that glucose attenuates deficits in paradoxical sleep and memory after atropine administration, with similar dose-response curves for both actions. In the first experiment, rats received saline, atropine (1 mg/kg), glucose (100 mg/kg) or combinations of atropine + glucose (10, 100, 250, and 500 mg/kg) 30 min before assessment on a spontaneous alternation task. In the second experiment, 3-h EEGs were assessed for spontaneous daytime sleep in rats administered saline, atropine (1 mg/kg), glucose (100 mg/kg) or combinations of atropine + glucose (10, 100 and 250 mg/kg). In both experiments, glucose significantly attenuated deficits at an optimal dose of 100 mg/kg. A third experiment assessed blood glucose levels after injections of atropine + glucose (100 mg/kg) and determined that blood glucose levels were similar to those produced by other treatments which enhance memory. These results are consistent with the view that paradoxical sleep and at least one test of memory are similarly influenced by atropine and glucose.     

Biosynthesis of the antibiotic actinorhodin. Analysis of blocked mutants of Streptomyces coelicolor

From two types of class V act mutants of Streptomyces coelicolor two monomeric precursors of actinorhodin have been isolated and their structures determined. One is the known antibiotic kalafungin and the other a new compound. Their relationship to actinorhodin biosynthesis is discussed.     

Variations in the use of diagnostic procedures after acute stroke in Europe: results from the BIOMED II study of stroke care

Valid classification of stroke is essential to initiate effective acute management and early secondary prevention strategies. To accurately evaluate stroke subtype a number of diagnostic procedures have to be performed. This study sought to investigate variations in use of diagnostic procedures across selected European hospitals. First-ever stroke patients were sampled over a 1-year period through 11 hospital-based registers across 10 European countries. We defined a diagnostic standard for valid aetiological classification of ischemic stroke including brain imaging, vascular imaging and echocardiography. The impact of socio-demographic, clinical and structural characteristics on performance of the diagnostic standard was assessed using multivariate logistic regression analyses. A total of 1721 patients were included in the study. 83.1% received brain imaging, ranging from 32.8% to 100%. The diagnostic standard was performed in 40.4% of stroke patients, ranging from 0% to 77.2%. Patients with increasing age ( P  < 0.001) and with more severe strokes ( P  = 0.001) were less probably to receive the diagnostic standard. Patients treated in stroke units and neurological departments were more frequently investigated with the diagnostic standard ( P  < 0.001). Less than half of hospitalized stroke patients across Europe underwent diagnostic procedures to allow for aetiological classification of stroke, which may hamper the initiation of effective early management and secondary prevention.     

Association of a 70-kDa tyrosine phosphoprotein with the CD16:ζ:γ complex expressed in human natural killer cells

The CD16: ζ: γ receptor complex allows natural killer (NK) cells to recognize and eliminate antibody-coated target cells. Whereas the ectodomain of CD16 is the receptor for Fcγ domains of immunoglobulins, disulfide-linked homo- and heterodimers composed of ζ and γ are required for the cell surface expression, and signal transduction properties of the complex. Engagement of CD16 activates the tyrosine kinase pathway, which induces the tyrosine phosphorylation of several substrates, including the ζ subunit and the phospholipase C γ-1 and γ-2 isoforms. Here we show that CD 16 stimulation of either peripheral blood NK cells, leukemic NK cells, or Jurkat transformants expressing a CD16:ζ:γ receptor complex, results in the tyrosine phosphorylation of a 70 kDa ζ-associated protein (pp70). Similarly, a 70-kDa ζ-associated phosphoprotein in T cells has been shown to be a tyrosine kinase (ZAP-70). Peptide mapping analysis indicates that the 70-kDa ζ-associated phosphoproteins from T cells and NK cells are structurally indistinguishable. We conclude that the CD16:ζ:γ complex may use a ZAP-70-related non-receptor tyrosine kinase, in the CD16 signaling cascade leading to NK cell activation.     

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND--The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS--The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS--Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS--Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.