Mutation screening of patients with Alzheimer disease identifies APP locus duplication in a Swedish patient

BACKGROUND: Missense mutations in three different genes encoding amyloid-β precursor protein, presenilin 1 and presenilin 2 are recognized to cause familial early-onset Alzheimer disease. Also duplications of the amyloid precursor protein gene have been shown to cause the disease. At the Dept. of Geriatric Medicine, Karolinska University Hospital, Sweden, patients are referred for mutation screening for the identification of nucleotide variations and for determining copy-number of the APP locus. METHODS: We combined the method of microsatellite marker genotyping with a quantitative real-time PCR analysis to detect duplications in patients with Alzheimer disease. RESULTS: In 22 DNA samples from individuals diagnosed with clinical Alzheimer disease, we identified one patient carrying a duplication on chromosome 21 which included the APP locus. Further mapping of the chromosomal region by array-comparative genome hybridization showed that the duplication spanned a maximal region of 1.09 Mb. CONCLUSIONS: This is the first report of an APP duplication in a Swedish Alzheimer patient and describes the use of quantitative real-time PCR as a tool for determining copy-number of the APP locus

Inhibition of the inositol kinase Itpkb augments calcium signaling in lymphocytes and reveals a novel strategy to treat autoimmune disease

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes. Pharmacological inhibition or genetic deletion of Itpkb results in elevated intracellular Ca2+ and induction of FasL and Bim resulting in T cell apoptosis. Deletion of Itpkb or treatment with Itpkb inhibitors blocks T-cell dependent antibody responses in vivo and prevents T cell driven arthritis in rats. These data identify Itpkb as an essential mediator of T cell activation and suggest Itpkb inhibition as a novel approach to treat autoimmune disease

IRRADIATIONS NEURO MENINGEES AU COURS DU TRAITEMENT DE LA LEUCEMIE LYMPHOBLASTIQUE AIGUE

The results achieved by neuromeningeal irradiation during the treatment of acute lymphoblastic leukemia are described. 22 children were prophylactically irradiated on a meningeal level. The factors facilitating radiotherapy were the youth of the patients, the early application of radiotherapy in the treatment of the disease, and the systematic association of irradiation and intrarachidial chemotherapy. The curative irradiation of 7 cases representing a neurologic symptomatology did not procure any valuable results.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

RADIOTHERAPIE DU MYCOSIS FONGOIDE

Radiotherapy is the palliative treatment of choice of fungoid mycosis, and is effective in about 90% of cases. The variety of the rays available makes it possible to adapt the treatment plan to each clinical situation, in particular to the density of the lesions. For those that are extensive but superficial, for example, electron baths at a dose of 2000 to 3000 rads procure a great number of complete remissions. The possibility of spreading these treatments without compromising their efficacy may notably facilitate their application. The existence of spontaneous remissions prevents overconfidence in attributing to the irradiations the cure of a few patients who have survived this treatment for more than 10 years. Nevertheless, some successes obtained by radiotherapy of lymph node lymphomas raises the hope that earlier recourse to it in more extensive regions, may exert a favourable influence on the survival of patients suffering from fungoid mucosis.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

INTERET DE LA TOMOGRAPHIE AXIALE COMPUTEE ET DE LA DOSIMETRIE PAR ORDINATEUR DANS LE TRAITEMENT DES TUMEURS DU MASSIF FACIAL

The combined use of the CAT (computed axial tomograph) and computer dosimetry allows better calculation of dose distribution in radiotherapy. Treatment plans can be calculated so rapidly that several may be drawn up until one with satisfactory dose distribution is achieved. In a first program, the dose distribution is given on a course matrix; owing to the rapidity of this conventional program and the possibilities of changing parameters, it renders it possible to seek the optimal solution for the treatment. A second, more exact program then puts into operation the solution found, and supplies documents that characterize the treatment plan, the irradiation protocol and the dose distribution, in the form of isodose curves. This combined method outlines the volumes to be treated, gives better insight into the arrangement of organs to be protected and allows evaluation of the variations of the absorption coefficients as a function of the density of the tissues through which the irradiation bundles pass. Accordingly, highly accurate treatment plans, optimally adjusted to the patient's condition may be drawn up. Also, the CAT by itself allows monitoring of the efficacy of the irradiations and regular surveillance of the irradiated site during the months after the end of the treatments.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Place de la radiothérapie dans le traitement des tumeurs étendues du larynx sus glottique

The clinical recovery obtained with conventional and high energy radiotherapy on advanced cancer of the larynx has been evaluated in 108 patients treated from 1955 to the end of 1970. The lesions were of stages T3 and T4, and in 35% of the cases were accompanied by cervical adenopathy. Fifty two patients were treated by conventional radiotherapy at 200 kV, 6000 to 6500 rads being applied in 2 opposed fields, as well as prophylactic irradiation of the supraclavicular regions. Of the 56 patients treated by high energy radiation, 50 were subjected to telecobalt, 6 to Betatron radiation. Similar rates of survival without relapse 3 yr after treatment were observed in both groups: 42.3% in patients treated by 200 kV, and 42.9% in patients treated by high energy radiation. While the use of high energy radiotherapy does not seem to improve survival, it does, nevertheless, avoid producing cutaneous lesions normally seen in treatment at a low energy. In 40 of the 108 patients (37%), laryngeal or ganglionary relapse was observed, the incidence being greater in patients having received conventional radiotherapy. Followup surgery was performed on 22 patients, 10 of whom have survived for 3 yr without any sign of subsequent evolution. If those patients cured by followup surgery and those deceased by intercurrent disease, in the absence of evolution of the cancer, are included in the statistics, the 3 yr survival rate changes from 42.5% to 56.5%.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

TRAITEMENT RADIOTHERAPIQUE DES TUMEURS LARYNGEES PAR SUPERVOLTAGE. ETUDE DES RESULTATS

87 patients with laryngeal carcinoma were treated by irradiation between 1963 - 1967, 80 with Cobalt and 7 by Betatron. The dose was 6700 to 7200 rads over a period of 6 to 7 weeks. Subglottic cancers comprised 61% and 50% were in grade T3 or T4. Thirty two patients were alive five years after treatment. Of the subglottic group 16(29%) were recurrence at five years. Laryngectomy was done in 10 of the 20 cases with local recurrence, and of these 3 survived five years. In the subglottic group, all the recurrences occurred within the first three years. An improvement in results is anticipated with an increase in the size of the fields irradiated. (Suggit - Queensland)SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Computed axial tomography (CAT) contribution for dosimetry and treatment evaluation in lung cancer

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

PACE DE LA RADIOTHERAPIE DANS LE TRAITEMENT POSTOPERATOIRE DES TUMEURS DE L'ESTOMAC

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Syndrome de pancoast et tumeurs bronchiques apicales. Revue de 30 patients analyse de la littérature et nouveau protocole thérapeutique

Thirty Pancoast syndromes related to pulmonary sulcus tumours are reviewed. Pain is poorly relieved by radiotherapy or palliative surgery. The mean survival rate is 10 months. We propose preoperative radiotherapy (3,500 rads) of localized tumours followed by extensive surgical resection after 4 weeks. Data from the literature and two initial cases are reported.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe