Rescue of influenza C virus from recombinant DNA.

The rescue of influenza viruses by reverse genetics has been described only for the influenza A and B viruses. Based on a similar approach, we developed a reverse-genetics system that allows the production of influenza C viruses entirely from cloned cDNA. The complete sequences of the 3' and 5' noncoding regions of type C influenza virus C/Johannesburg/1/66 necessary for the cloning of the cDNA were determined for the seven genomic segments.

Failure of zanamivir therapy for pneumonia in a bone-marrow transplant recipient infected by a zanamivir-sensitive influenza A (H1N1) virus.

Influenza A viruses are responsible for significant morbidity and mortality after bone marrow transplantation. Here we report failure of inhaled zanamivir treatment in a bone-marrow transplant recipient with pneumonia caused by an influenza A (H1N1) virus, although the influenza viruses isolated from bronchoalveolar lavages before and after treatment were clearly found to be sensitive to zanamivir using cell-based and enzymatic assays. Subsequent oral treatment with oseltamivir allowed complete recovery.

Random-mood interpretation of determinants for major depression.

Background: It has recently been proposed that major depression disorder (MDD) may, in a heterogeneous population-based cohort, be interpreted in terms of a random-mood model. Mood fluctuations are thought to result from stressors that occur randomly in time. We have investigated whether this concept also holds for more homogeneous groups, defined by known determinants for MDD, and whether the model's parameters, susceptibility (Z) and relaxation time (T), may be evaluated and used to differentiate between subcohorts.

Absence of detection of highly pathogenic H5N1 in migratory waterfowl in southern France in 2005-2006.

During fall 2005, the rapid and wide spread of highly pathogenic (HP) H5N1 avian influenza viruses (AIV) outside Asia alerted European health authorities. Because of abnormal and recurrent field mortality, wild migratory birds were considered to be the main dispersing agent of the virus at an intercontinental scale. European wintering wetlands, such as the Camargue (Rhône delta, France), are identified as potential hot spots for the risk of introduction and transmission of bird-borne diseases.

Influenza A/H5N1 virus infection in humans in Cambodia.

Background: Between January 2005 and April 2006, six patients of influenza A/H5N1 virus infection were reported in Cambodia, all with fatal outcome.

Objectives: We describe the virological findings of these six H5N1 patients in association with clinical and epidemiologic findings.

Study Design: Broncho-alveolar lavage, nasopharyngeal, throat and rectal swabs and sera were cultured for virus isolation and viral load quantified in clinical specimens by real-time RT-PCR.

Cognitive performance after mild traumatic brain injury: the impact of poor effort on test results and its relation to distress, personality and litigation.

Primary Objective: To compare consecutive Mild Traumatic Brain Injury (MTBI) patients with and without adequate effort on cognitive performance, litigation status, fatigue, distress and personality.

Research Design: (Neuro)psychological assessment was done 6 months post-injury in 110 patients from a cohort of 618 consecutive MTBI patients aged 18-60, who attended the emergency department of our level I trauma centre. Effort was tested with the Amsterdam Short Term Memory test.

Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS.

The SARS-CoV spike glycoprotein (S) is the main target of the protective immune response in humans and animal models of SARS. Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). The presence of both splice sites and WPRE markedly improved the immunogenicity of S-based DNA vaccines against SARS.

Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells.

The transcription/replication activity of ribonucleoproteins derived from influenza A primary isolates of human (A/Paris/908/97) or avian origin (A/Mallard/Marquenterre/MZ237/83, A/Hong Kong/156/97) was compared upon reconstitution in mammalian or avian cells, using viral-like reporter RNAs synthesized under the control of the human and chicken RNA polymerase I promoters, respectively. In avian cells, transcription/replication activities were in the same range with all ribonucleoproteins tested. In human cells, ribonucleoproteins derived from A/Mallard/Marquenterre/MZ237/83 showed reduced transcription/replication activity and reduced NP binding to the PB1-PB2-PA complex (P) or to the isolated PB2 subunit, as compared to the ribonucleoproteins derived from A/Paris/908/97.

Writer's cramp: restoration of striatal D2-binding after successful biofeedback-based sensorimotor training.

Introduction: Previous studies of writer's cramp have detected cerebral sensorimotor abnormalities in this disorder and, more specifically, a reduced striatal D2-binding as assessed by [(123)I]IBZM SPECT. However, empirical data were lacking about the influence of effective biofeedback-based sensorimotor training on D2 receptor binding.

Methods: To determine whether there is a restoration of D2-binding after successful sensorimotor treatment, pre- and posttreatment SPECTs were compared in five patients with writer's cramp and correlated with improvement in handwriting.

Humoral and cellular responses to influenza vaccination in human recipients naturally tolerant to a kidney allograft.

Rare kidney allograft recipients enjoy unaltered graft function years after interruption of their immunosuppressive treatment. To assess the extent to which this state of 'operational tolerance' (TOL) is specific to the graft and not the result of a global immunodeficiency, we analyzed the response of such patients following influenza vaccination. Hemagglutination inhibition titers and frequency of IFNgamma-secreting T cells were measured before 1 and 3 months after vaccination.

Inter- and intra-variant genetic heterogeneity of human coronavirus OC43 strains in France.

Human coronavirus OC43 (HCoV-OC43) causes acute, self-limited respiratory infections. A close relationship between bovine coronaviruses (BCoVs) and HCoV-OC43 has recently been demonstrated. This study includes seven clinical, non-cell culture-adapted, contemporary HCoV-OC43 strains detected in France in 2003.

Impact of additional extracranial injuries on outcome after mild traumatic brain injury.

Many patients with mild traumatic brain injury (MTBI) concurrently sustain extracranial injuries; however, little is known about the impact of these additional injuries on outcome. We assessed the impact of additional injuries on the severity of postconcussional symptoms (PCS) and functional outcome 6 months post-injury. A questionnaire (including the Rivermead Post-Concussion Questionnaire and SF-36) was sent to consecutive MTBI patients (hospital admission Glasgow Coma Score 13-15; age range 18-60 years) admitted to the emergency department of a level-I trauma center, and, to serve as a baseline for PCS, a control group of minor-injury patients (ankle or wrist distortion).

Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to oseltamivir.

Geographic spread of highly pathogenic avian H5N1 influenza viruses may give rise to an influenza pandemic. During the first months of a pandemic, control measures would rely mainly on antiviral drugs, such as the neuraminidase (NA) inhibitors oseltamivir and zanamivir. In this study, we compare the sensitivities to oseltamivir of the NAs of several highly pathogenic H5N1 viruses isolated in Asia from 1997 to 2005.

Autoimmune pancreatocholangitis: a series of ten patients.

Background: During a 10-year period we observed 10 patients who suffered from an inflammatory-fibrosing disease mimicking pancreatic carcinoma and primary sclerosing cholangitis (PSC).

Methods: A review of the presenting features, the clinical course and the relevant literature.

Results: Ten male patients (mean age 55 years) presented with weight loss, jaundice and pruritus.

Programme of the Community Network of Reference Laboratories for Human Influenza to improve Influenza Surveillance in Europe.

All laboratories participating in the Community Network of Reference Laboratories for Human Influenza in Europe (CNRL) co-ordinated by the European Influenza Surveillance Scheme (EISS) should be able to perform a range of influenza diagnostics. This includes direct detection, culture, typing, subtyping and strain characterisation of influenza viruses, diagnostic serology and the creation of archives for clinical specimens and virus isolates. To improve the capacity and quality of the laboratories of the CNRL and to increase the consistency in performance among all 25 European Union countries plus Norway, Romania, and Switzerland, five task groups were set up in February 2005.

Central adaptations during repetitive contractions assessed by the readiness potential.

Physiological fatigue, a loss of maximal force producing capacity, may originate both from changes at the peripheral and at the central level. The readiness potential (RP) provides a measure to study adaptations to physiological fatigue at the motor cortex. We have studied the RP in the course of repetitive contractions at a high force level.

Recovery from mild traumatic brain injury: a focus on fatigue.

Background: Fatigue is one of the most frequently reported symptoms after Mild Traumatic Brain Injury (MTBI). To date, systematic and comparative studies on fatigue after MTBI are scarce, and knowledge on causal mechanisms is lacking.

Objectives: To determine the severity of fatigue six months after MTBI and its relation to outcome.

Major depressive episodes and random mood.

Context: Mathematical models describing changes in mood in affective disorders may assist in the identification of underlying pathologic and neurobiologic mechanisms and in differentiating between alternative interpretations of psychiatric data.

Objective: Using time-to-event data from a large epidemiologic survey on recovery from major depression, to model the survival probability, in terms of an underlying process, with parameters which might be recognized and influenced in clinical practice.

Design: We present a sequential-phase model for survival analysis, which describes depression as a state with or without an additional incubation phase.

[Research and development of reverse genetics for influenza viruses].

Influenza viruses have long been refractory to reconstitution from cloned cDNAs, likely because of the properties of their genome : segmented and negative-stranded RNA, infectious only if in association with the nucleoprotein and polymerase complex. In the late 90s, by relying on an RNA polymerase I dependent transcription system and by cotransfecting 12 or 8 plasmids, reconstitution of the eight ribonucleoproteins of an influenza A virus in a cell was achieved, and production of recombinant viruses was finally obtained. Plasmidbased reverse genetics systems are now widely used to study the molecular mechanisms of virus replication and pathogenicity.

Recombinant influenza A viruses harboring optimized dicistronic NA segment with an extended native 5' terminal sequence: induction of heterospecific B and T cell responses in mice.

We generated novel recombinant influenza A viruses (vNA38) harboring dicistronic NA segments with an extended native 5' terminal sequence of 70 nucleotides comprised of the last 42 nucleotides of the NA ORF and the 5' noncoding region (5' NCR). vNA38 viruses replicated stably and more efficiently than vNA35 viruses with a dicistronic NA segment comprised of the native 5' NCR only, that we described previously (Vieira Machado, A., Naffakh, N.

Cloning of the chicken RNA polymerase I promoter and use for reverse genetics of influenza A viruses in avian cells.

Reverse genetics techniques to rescue influenza viruses have thus far been based on the use of a human polymerase I (PolI) promoter to direct the synthesis of the eight viral RNAs. They can only be used on cells from primate origin due to the species specificity of the PolI promoter. Here we report the cloning of the chicken PolI promoter sequence and the generation of recombinant influenza virus upon transfection of bidirectional PolI/PolII plasmids in avian cells.

The toboggan sun.

Special variants of the Novaya Zemlya effect may arise from localized temperature inversions that follow the height profile of hills or mountains. Rather than following its natural path, the rising or setting Sun may, under such circumstances, appear to slide along a distant mountain slope. We found early observations of this effect in the literature by Willem Barents (1597) and by Captain Scott and H.