Search

Objectives The Sensio study objectives were to assess the outcome of neuropsychiatric adverse reactions (NPAR) that develop after initiation of efavirenz (EFV) therapy, to ascertain the late NPAR after a 3-month treatment period, to evaluate the impact of NPAR on patients' quality of life (QoL) in a real-life population. Methods During a 6-month period, consecutive HIV-infected adult outpatients receiving an ongoing EFV therapy for at least 3 months were asked to fill in a specifically designed self-administered questionnaire addressing sleep disturbances, behavioural changes, mood disturbances, anxiety, cognitive disorders, hallucinations, dizziness and the general impact on patients' QoL. Results A total of 174 questionnaires were analyzed. The main late emergent NPAR were sleep disorders: abnormal dreams 24.7%, nocturnal waking 19.6%, trouble falling asleep 17.8%; cognitive disorders: memory disorders 23.0%, impaired concentration 18.9%; anxiety 15.5%; mood disorders: sadness 19.3%, suicidal ideations 9.2%. Global neuropsychic discomfort was moderate to severe in 23% of patients after a 3-month treatment period. Conclusion NPAR occur mainly during the first month of EFV therapy but often persist thereafter. A significant percentage of patients reported suicidal ideations at the time of the study. Our results suggest the need for routine screening for NPAR among patients receiving EFV therapy and better management. [ABSTRACT FROM AUTHOR]

We have applied an automated real‐time quantitative PCR assay using a double‐labeled fluorogenic probe to detect t(9;22)‐positive cells in haematological malignancies. The results are expressed as the ratio of chimeric bcr‐abl transcripts on abl transcripts. Highly reproducible results were obtained for t(9;22)‐positive K562 RNA. Ten copies of bcr‐abl DNA from a recombinant KW‐3 plasmid and one positive cell in 104 can be detected. Thirty‐two patients with chronic myeloid leukaemia (CML), 25 with acute leukaemia, 12 with myelodysplastic syndromes and 7 with other myeloproliferative syndromes were tested. Follow‐up data were obtained in bcr‐abl positive cases. Results were compared with those of conventional nested RT‐PCR and cytogenetics. Real‐time quantitative RT‐PCR values correlated well with both these methods. However, in some cases the only means of detecting early relapse or blastic transformation was to examine the kinetics of real‐time quantitative RT‐PCR. Thus, real‐time quantitative RT‐PCR appears suitable for the diagnosis and follow‐up of patients with the t(9;22) translocation. [ABSTRACT FROM AUTHOR]

Porcine peripheral blood mononuclear cells (PBMC) are induced to produce interferon alpha (IFNα) following in vitro exposure to coronavirus TGEV (transmissible gastroenteritis virus)-infected glutaraldehyde-fixed cell monolayers or lo TGEV virions. In the present report, we examined the possibility that glycosylation of viral proteins could play a major role in interactions with PBMC leading to the production of IFNα. Con A pretreatment of TGEV-infected cell monolayers before fixation with glutaraldehyde and exposure to PBMC caused a dose-dependent inhibition of IFNα induction, implying that masking of carbohydrates at the surface of infected cells lowered IFN-α-induction. Similarly, inhibition of N-linked glycosylation by tunicamycin during viral infection of cell monolayers altered their ability to induce IFNα. In addition, complete cleavage of 'complex type' oligosaccharides by peptide-N-glycohydrolase F lowered the capacity of TGEV virions to induce IFNα. Thus, these findings strongly suggest that glycosylation of the viral proteins, and more precisely the presence of complex-type oligosaccharides, is an important requirement for a completely efficient interaction with PBMC leading lo the production of IFN-α. [ABSTRACT FROM AUTHOR]

In viruses belonging to the Birnaviridae family, virus protein 4 (VP4) is the viral protease responsible for the proteolytic maturation of the polyprotein encoding the major capsid proteins (VP2 and VP3). Infectious pancreatic necrosis virus (IPNV), the prototype of the aquabirnavirus genus, is the causative agent of a contagious disease in fish which has a large economic impact on aquaculture. IPNV VP4 is a 226-residue (24.0 kDa) serine protease that utilizes a Ser/Lys catalytic dyad mechanism (Ser633 and Lys674). Several truncated and mutant forms of VP4 were expressed in a recombinant expression system, purified and screened for crystallization. Two different crystal forms diffract beyond 2.4 A resolution. A triclinic crystal derived from one mutant construct has unit-cell parameters a = 41.7, b = 69.6, c = 191.6 A, alpha = 93.0, beta = 95.1, gamma = 97.7 degrees. A hexagonal crystal with space group P6(1)22/P6(5)22 derived from another mutant construct has unit-cell parameters a = 77.4, b = 77.4, c = 136.9 A.

Blotched snakehead virus (BSNV) is a member of the Birnaviridae family that requires a virally encoded protease known as VP4 in order to process its polyprotein into viral capsid protein precursors (pVP2 and VP3). VP4 belongs to a family of serine proteases that utilize a serine/lysine catalytic dyad mechanism. A mutant construct of VP4 with a short C-terminal truncation was overexpressed in Escherichia coli and purified to homogeneity for crystallization. Using the sitting-drop vapour-diffusion method at room temperature, protein crystals with two distinct morphologies were observed. Cubic crystals grown in PEG 2000 MME and magnesium acetate at pH 8.5 belong to space group I23, with unit-cell parameters a = b = c = 143.8 angstroms. Trigonal crystals grown in ammonium sulfate and glycerol at pH 8.5 belong to space group P321/P312, with unit-cell parameters a = b = 158.2, c = 126.4 angstroms.