Induction of Bcl-xL-specific cytotoxic T lymphocytes in mice.

The induction of active immunity against tumour-associated antigens to prevent relapse of cancer is a promising approach but has so far shown only low efficacy. This low efficacy may in part be due to clonal escape of tumour cell variants by the downregulation of antigen expression or inflammation-induced dedifferentiation. Identification of novel tumour-associated antigens that at the same time are essential for continued tumour cell survival is thus critical for the development of active cancer vaccinations. At the same time, identification of novel endogenous murine tumour antigens will help improve preclinical development of cancer immunotherapy. The anti-apoptotic protein Bcl-xL has been suggested to be such an essential tumour antigen, but the lack of well-defined murine epitopes have delayed preclinical studies of Bcl-xL-targeting cancer vaccines. Here, we report the identification of two novel murine tumour-associated epitopes TAYQSFEQV and AFFSFGGAL derived from mouse Bcl-xL. Dendritic cell (DC)-based vaccination induced CD8(+) T cells capable of producing IFN-γ upon restimulation with these epitopes. Thus, our data may benefit the design of future immunotherapy strategies by providing a preclinical model for cancer vaccination with an endogenous tumour antigen that can be combined with other cancer treatments.

Adverse effects associated with high-dose olanzapine therapy in patients admitted to inpatient psychiatric care.

CONTEXT: In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units. METHODS: The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population. RESULTS: The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death. CONCLUSION: Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.

[Antikeratin antibodies in rheumatoid arthritis]. / Antikeratin-antistoffer ved reumatoid arthritis.

On the basis of the literature and the author's own investigations the present knowledge about antikeratin antibodies (AKA) in rheumatoid arthritis (RA) is summarized. The specificity of AKA for RA is described between 90% and 100%, but the sensitivity is reported as varying from 36% to 80%. In conclusion, AKA have great diagnostic value in RA and, high titre AKA, were found to be pathognomonic for RA. Further studies are necessary to confirm if AKA are also of prognostic and pathogenetic value in RA.

[Rhesus immunization in a rhesus-positive pregnant woman: fetal erythroblastosis caused by the rhesus antibody anti-C]. / Rhesusimmunisering hos rhesus-positiv gravid: erythroblastosis foetalis forårsaget af rhesusantistoffet anti-C.

A rhesus-D-positive woman aged 32 years with two previous pregnancies was delivered of an infant with erythroblastosis foetalis caused by the rhesus antibody anti-c produced by alloimmunization during pregnancy. Screening for antibodies in the 12th week of pregnancy yielded negative results. No screening was undertaken in the 35th week of pregnancy. The infant was born with severe anaemia. Following delivery, the anti-c alloimmunization was diagnosed and three exchange transfusions were administered. On the fourth day of life, the infant developed the inspissated bile syndrome. No cerebral disorders were demonstrated. Antibody screening of rhesus-positive women has now been introduced at the 35th week of pregnancy to avoid similar cases.

Teratogenic effects of retinoic acid and dimethylsulfoxide on embryonic chick wing and somite.

In order to document the stage(s) at which the embryonic chick wing bud is sensitive to vitamin A teratogenesis and the kinds of defects produced by vitamin A insult to the embryonic chick wing, 1-microgram doses of retinoic acid (1 microliter RA in 90% DMSO at a concentration of 1 microgram/microliter) were locally applied to the right wing bud of chick embryos at stages 17-23 (Hamburger and Hamilton: J. Morphol., 88:49-92, '51), and the resulting limb skeleton anatomy was observed at 10 days of incubation. Local application of RA at stages 17-20 resulted in distal wing skeleton defects. There were significantly more wing skeleton defects among embryos treated at these stages with RA solution than among solvent (DMSO)-treated control embryos and than among untreated control embryos. Wings of embryos treated with RA at stages 21-23 were always normal. Scapular and vertebral defects were seen at 10 days of incubation among embryos which had been treated prior to stage 21 with both the RA solution and the solvent control. Statistical analysis and histological data suggest that scapular and vertebral defects were caused by DMSO-induced damage to somites.