Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report

Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA

Revisiting the Effect of Acute P. falciparum Malaria on Epstein-Barr Virus: Host Balance in the Setting of Reduced Malaria Endemicity

Burkitt's lymphoma (BL), an EBV-associated tumour, occurs at high incidence in populations where malaria is holoendemic. Previous studies in one such population suggested that acute P.falciparum infection impairs EBV-specific T-cell surveillance, allowing expansion of EBV infected B-cells from which BL derives. We re-examined the situation in the same area, The Gambia, after a reduction in malaria endemicity. Cellular immune responses to EBV were measured in children with uncomplicated malaria before (day 0) and after treatment (day 28), comparing EBV genome loads in blood and EBV-specific CD8+ T-cell numbers (assayed by MHC Class I tetramers and IFNγ ELISPOTS) with those seen in age- and sex-matched healthy controls. No significant changes were seen in EBV genome loads, percentage of EBV-specific CD8+ T-cells and IFNγ producing T-cells in acute versus convalescent samples, nor any difference versus controls. Regression assays performed also no longer detected any impairment of EBV-specific T-cell surveillance. Acute uncomplicated malaria infection no longer alters EBV-specific immune responses in children in The Gambia. Given the recent decline in malaria incidence in that country, we hypothesise that gross disturbance of the EBV-host balance may be a specific effect of acute malaria only in children with a history of chronic/recurrent malaria challenge

Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation

Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1

Detection of Epstein-Barr virus (EBV) in human lymphoma tissue by a novel microbial detection array

BACKGROUND: Infectious agents are estimated to play a causative role in approximately 20% of cancers worldwide. Viruses, notably the Epstein-Barr virus (EBV), are associated with 10-15% of B-cell lymphomas and are found at a higher frequency in immunosuppressed patients. In this study, we screened human lymphoma tissues using a novel Lawrence Livermore Microbial Detection Array (LLMDA), a comprehensive detection system that contains probes for all sequenced viruses and bacteria. This technology has been applied to identify pathogen-associated diseases. RESULTS: We evaluated samples from 58 cases with various lymphoid tissue disorders using LLMDA. These included 30 B-cell lymphomas (9 indolent and 21 aggressive type), 2 T-cell lymphomas and 2 NK/T cell lymphomas, 4 plasmacytomas as well as 8 specimens of benign lymphoid tissue. Five of 21 high-grade B-cell lymphomas were positive for Epstein-Barr virus-encoded small RNA (EBER+), while all the indolent B-cell lymphomas were EBER-. Similarly, both NK/T cell lymphomas were EBER+, and the benign tissues were EBER-. We also screened 10 cases of post-transplant lymphoproliferative disorder (PTLD). Five of these cases (4 B-cell lymphomas and 1 NK/T cell lymphoma) were EBER+, and the remaining five cases were EBER-. CONCLUSIONS: We have confirmed the reliability of the LLMDA methods by detecting EBV in EBV-positive lymphomas while observing no false-positive results in EBV-negative lymphomas. The LLMDA technique provides a sensitive and alternative method for identifying known viral pathogen associated with tumors and may prove useful for future clinical identification of novel cancer-associated viral pathogens

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509

Light paintings

Opinnäytetyössäni käsittelen omaa taiteellista tuotantoani. Aluksi kerron kuinka olen päätynyt tekemään sitä mitä teen ja esittelen kuvasarjani. Tämän jälkeen käyn läpi käsitteitä, jotka liittyvät työhöni. Oma työskentelyni on kehittynyt kohti valon kuvaamista. Kuvaan valoa tietyn ajan kuluessa tai aikaa tietyssä valossa. Miten päin asiaa haluaakaan ajatella. Tutkin valon luonteita vuorokauden- ja vuodenaikojen muutoksina. Kuinka erilainen valo on eri aikoina? Miten se muuttaa kohdettaan? Ja kuinka se suhteutuu ympäristön väreihin? Tekstissäni perehdyn valoon Claude Monetin kautta. Kävelyllä on ollut tärkeä merkitys teosteni synnylle. Se toimii inspiraation lähteenä ja oli merkittävässä roolissa ensimmäisissä sarjoissani. Käsittelen kävelyn teemaa Richard Longin työskentelyn avulla. Aika, vuodenajat, toisto ja sattuma, sekä valokuvauksen ja maalauksen suhde ovat aiheina seuraavissa luvuissa. Käyn näitä asioita läpi taiteilijoiden avulla, joiden teoksiin ja työskentelyyn olen tutustunut kirjoittaessani tätä lopputyötä. Yhteistä kaikille valitsemilleni taiteilijoille tai teoksille on pitkien ajanjaksojen käyttäminen. Muita yhdistäviä tekijöitä ovat työskentelymetodit, tekniikka tai visuaalinen lopputulos

Extranodal NK/T-cell lymphoma, nasal type extensively involving the bone marrow

Extranodal NK/T-cell lymphoma, nasal type, is an aggressive EBV-associated lymphoma that mainly involves the nasal cavity but has also been reported to involve other extranodal sites without nasal involvement. In contrast to aggressive NK cell leukemia (a marrow-based aggressive leukemia of NK-cell origin); extensive bone marrow and blood involvement is extremely uncommon by nasal type NK/T lymphoma. We report a patient with extranodal NK/Tcell lymphoma, nasal type that developed extensive bone marrow involvement during the course of her disease with some overlapping features with aggressive NK-cell leukemia