Bulletin et memoires de l'Academie royale de medecine de Belgique最新文献

Allogeneic haematopoietic stem cell transplantation is the best treatment option for many patients suffering from severe haematologic diseases. Allogeneic transplantation is generally preceded, by a myeloablative conditioning regimen consisting of high doses of chemo/radiotherapy. The use of those high dose conditionings is restricted to young patients (< 55 years of age) without significant comorbidities. Unfortunately, median patient age at diagnosis of most haematological malignancies ranges from 60 to 70 years. It has been accepted since the late 1970s that the occurrence of acute and/or chronic graft-versus-host disease (a life-threatening complication of allogeneic transplantation consisting of host organ destruction by donor T cells present in the graft) leads to a dramatic decreased risk of relapse thanks to the destruction of host tumour cells by donor T cells (graft-versus-tumour effects). These observations led several groups of investigators to develop non-myeloablative conditionings for allogeneic haematopoietic stem cell transplantation (also termed mini-transplant) based nearly exclusively on graft-versus-tumour effects for tumour eradication. After a brief introduction, this article reviews preliminary results of nonmyeloablative transplantation and then present some perspectives aimed at increasing the efficacy while decreasing the toxicity of this approach.

The emergence of Bluetongue, due to the virus of serotype 8 (BTV-8) was an unexpected event in Belgium. This vector-borne disease is caused by a virus belonging to the family of Reoviridae, genus Orbivirus whose genome consists of 10 double-stranded RNA segments. During this emergence, the virulence of the BTV-8 was exacerbated in bovines and was expressed by the appearance of severe clinical signs and reproductive disorders. The contribution of the Unit of research in epidemiology and risk analysis applied to veterinary sciences (UREAR-U.Lg.) consisted of the description, the understanding and the analysis of the particular profile which was observed during this emergence. This understanding required both field studies and a series of experimental infections in high containment facilities. Overall, emergent animal diseases have been of particular importance these last few years and represent unprecedented health, socio-economic, international, biological, partnership and media challenges.

Prostate cancer is the most prevalent cancer in men aged fifty or more. Resulting mortality, however, is low since most prostatic cancers are slow-growing, non-lethal tumours. The introduction of PSA screening has profoundly impacted on the epidemiology of prostate cancer. Men bearing aggressive disease are diagnosed sooner so that radical treatment can be applied more effectively. But PSA screening also unveil many indolent cancers that would have not threaten the patient if left undiscovered. Systematic treatment of indolent cancers may result into many men being exposed to unwanted side effects. For this reason, the true benefit of PSA screening is still a matter of intense debate. Nevertheless, there is room for an ethical approach of prostate cancer screening, based on information, correct identification of aggressive disease and early integration of new biomarkers.

Our work aims at the identification of new diagnostic and prognostic markers in rheumatoid arthritis (RA), using synovial biopsies in patients. We first demonstrated that the molecular signatures identified in these biopsies enable us to differentiate patients with early RA from patients suffering from other inflammatory conditions. Next, we performed transcriptomic studies in synovial biopsies harvested from patients with severe RA before and twelve weeks after initiation of TNF blocking or rituximab (depleting anti-CD20 antibody) therapy. These studies enabled us to identify specific molecular signatures targeted by these therapies in the synovium, and novel markers of response to therapy. Our results open interesting perspectives in terms of potential biomarkers, which could be used in order to improve diagnostic performances and therapeutic decisions based on individual molecular characteristics of the patients.

In the contemporary biomedicine, the new medicines and technologies can be used not only to cure the patients but also to enhance human capacities: genetic design, alteration of cognitive and emotional functions, increase in life-span, or to boost performances in sport... This evolution represents a paradigmatic change in the medical practice. It is not the mere restoration of health which is expected anymore. What is required is "the perfectibility of the human being". In this article, the emergence of the "enhancement technologies" is examined from an ethical and philosophical perspective.

The introduction of new sequencing technologies is revolutionizing virus discovery and providing a new means to demonstrate the safety of vaccines. Since these methods do not depend on prior assumptions of the types of viruses that may be present, they have detected viruses missed by other methods like degenerate or, family specific, PCRs. We have used massively parallel sequencing (MP-Seq) to detect new viruses in bovine serum and in the faeces of animals. When applied to sequencing the transcriptome, MP-Seq can reveal latent or silent infections. While the sequencing technology is impressive, it is bioinformatics that is the key to its successful application.

The potentialities of nonaqueous capillary electrophoresis for chiral analysis were demonstrated through many pharmaceutical and biomedical applications, such as the stereoselective assay of acidic and basic drugs in plasma and urine as well as in vitro metabolism studies. A fundamental aspect of the quality control of chiral drugs in single-isomer forms, i.e. the enantiomeric purity determination, was also investigated. Moreover, the mechanisms of intermolecular interactions involved in the chiral separations observed in nonaqueous systems were elucidated using nuclear magnetic resonance.

Angelman syndrome is a neurogenetic disorder characterized by developmental delay, absence of speech, motor impairment, exuberant and happy demeanour and epilepsy. It may be caused by various abnormalities of chromosome 15q11-13 affecting the expression ofa gene whose multiple function still need to be clarified. Precise diagnosis carries clinical and genetic counselling implications. However, many clinicians still seem unfamiliar with it, despite the severity and typical aspects of presentation. Beyond individual situations, Angelman syndrome can serve as a paradigm for clinical and basic research into genetic and epigenetic influences in neurology, neurological development, motor control, behavioural phenotypes and epileptic syndromes. Recent advances in molecular biology and animal models of the syndrome provide new data which must be included in our interpretation of Angelman syndrome.

The plasmacytoid dendritic cells (pDCs) belong to the innate immune system and are responsible for the production of type interferons (IFN-I). These are crucial for the antiviral and antitumoral responses of the organism. Newborns are unable to produce IFN-I in response to viral infections, due to the absence of nuclear translocation of the transcription factor IRF7 in their pDCs. We have shown that this defect is due to the deficient phosphorylation of this factor, and that the PI3K-Akt-mTOR-pathway, on the other hand is functional. We have also shown, this time in adult pDCs, that the PI3K-Akt-mTOR-pathway, known to be absolutely necessary for the production of IFN-I in response to TLR9-ligands and RNA viruses, is surprisingly not required for this production in response to synthetic TLR7 ligands. These ligands are used in the clinic as vaccine adjuvants, antiviral and antitumoral agents. The inhibitors of PI3K and + mTOR are in use as immunosuppressors and adjuvants for chemotherapy, making these interactions clinically highly relevant.

The squamous cell carcinomas of the upper aero-digestive tracts are frequent cancers, with as much as 466831 and 168368 cases diagnosed in 2008 among men and women in the world, respectively. As such, they make up the sixth most frequent neoplasia among men and the eighth among women. Their frequency shows interesting variations covering the last twenty years, with an ascending tendency among women, which is maximal in Europe, and a descending tendency in men, maximal in the USA. The comparison with the Belgian official data reveals a striking elevation of incidence of these cancers among both sexes. Although the causal link between high-risk HPVs and cervical carcinoma is well-established, the implication of this viral infection in HNSCC remains debatable. 5 % to 65 % of head and neck cancers could be associated with oncogenic HPVs, in particular HPV type 16. The oropharynx--more precisely the tonsil--is the head and neck location presenting the highest incidence of HPV infection. Moreover, a clear increase of tonsillar carcinoma incidence has been described. As observed in cervical carcinomas, HPV positive HNSCCs are sexually transmitted and characterized by alterations of p53 and pRb signalling pathways. New studies regarding HPV status in HNSCCs are warranted to provide a rationale for large scale HPV vaccination in young male populations.