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Biomedical subjects

Dimitrios Papaioannou

Publications and source records attributed to Dimitrios Papaioannou.

5 recordsLinked to original sources

The common murine retroviral integration site activating Hhex marks a distal regulatory enhancer co-opted in human early T-cell precursor leukemia.

The Hhex gene encodes a transcription factor that is important for both embryonic and post-natal development, especially of hematopoietic tissues. Hhex is one of the most common sites of retroviral integration in mouse models. We found the most common integrations in AKXD (recombinant inbred strains) T-ALLs occur 57-61kb 3' of Hhex and activate Hhex gene expression. The genomic region of murine leukemia virus (MLV) integrations has features of a developmental stage-specific cis regulatory element (CRE), as evidenced by ATAC-seq in murine progenitor cells and high H3K27 acetylation at the syntenic CRE in human hematopoietic cell lines. With ChIP-exonuclease, we describe occupancy of LIM domain binding protein 1 (LDB1), the constitutive partner of the LIM Only-2 (LMO2), GATA1, and TAL1 transcription factors at GATA sites and at a composite GATA-E box within the CRE. With virtual 4C analysis, we observed looping between this +65kb CRE and the proximal intron one enhancer of HHEX in primary human ETP-ALLs and in normal progenitor cells. Our results show that retroviral integrations at intergenic sites can mark and take advantage of CREs. Specifically, in the case of HHEX activation, this newly described +65kb CRE is co-opted in the pathogenesis of ETP-ALL by the LMO2/LDB1 complex.

Humans↗

Expression of the RNA-binding protein CRD-BP in brain and non-small cell lung tumors.

The coding region determinant-binding protein (CRD-BP) is an RNA binding protein that recognizes c-myc and IGF-II leader 3 mRNAs as well as the oncofetal H19 RNA. CRD-BP exhibits an oncofetal pattern of expression and has been detected in the majority of colon (81%), breast (58.5%) and sarcoma (73%) tumors. The study of CRD-BP expression was extended in brain tumors and Non small cell lung (NSCL) carcinomas and 12/24 malignant, 2/5 benign neuroepithelial tumors and 4/15 of NSCL carcinomas were found positive. All normal matching tissues tested were found negative. The highest frequency (60%) of CRD-BP positive tumors was observed in meningiomas, either benign (11/18) or atypical (3/3). These findings confirm that CRD-BP expression is restricted in tumors; the frequency of its de novo expression may vary according to tumor type and appears to be an early event in the transformation process.

Adenocarcinoma↗

IgE-mediated sensitization in seafood processing workers.

Occupational-related allergic sensitization has been reported in fishery workers. The aim of this study was to investigate the prevalence, work-related symptoms, and possible risk factors in this occupationally exposed population in Greece. Sixty-four fish and seafood processing workers were compared with 60 controls regarding sensitization to seafood allergens. All participants underwent skin-prick tests (SPTs) with cod, sardines, shrimp, spiny lobster, crabs, salmon, mussels, and trout plus negative and positive control. The level of specific IgE (radioallergosorbent test) was evaluated in subjects with positive SPTs. Sensitization criteria were both SPTs and the corresponding positive radioallergosorbent test. Atopic status was tested with SPTs to seven common inhalant allergens. Potential risk factors for IgE sensitization were investigated using logistic regression analysis. Twenty-three of 64 workers (35.9%) were sensitive to at least one of the seafood allergens tested, and the prevalence in the control group was 10% (6/60; odds ratio, 5.049; 95% CI, 1.884-13.533). The prevalence of sensitization in allergen species tested in the fishery workers group was shrimp, 12.5%; spiny lobster, 10.9%; mussels, 7.8%; crabs 3.1%; cod, 3.1%; sardines, 1.6%; salmon, 1.6%; and trout, 1.6%. Presence of atopy (p = 0.02), intensity (p = 0.03), and duration of exposure (p = 0.03) was found as potential risk factors for IgE sensitization. Four of 64 (6.25%) workers reported work-related symptoms. Occupational exposure to fish and seafood significantly increases the likelihood of sensitization in seafood allergens and atopy, duration, and intensity of exposure may represent potential risk factors in seafood processing workers.

Adult↗

Pattern of sensitization to honeybee venom in beekeepers: a 5-year prospective study.

Beekeepers are at increased risk for honeybee (Hb) venom allergy and they represent a unique population for Hymenoptera venom studies. The aim of this was to prospectively examine the pattern of Hb venom sensitization over a 5-year period in new beekeepers and define possible predisposing factors. Thirty-five beekeepers were tested every 6 months for 5 years with in vivo and in vitro methods to detect the possible development of sensitization to Hb and common wasp (Cw) venom. Inclusion criteria included the lack of previous beekeeping activity and absence of sensitization or reported reaction to Hymenoptera stings. Subjects with both in vivo and in vitro tests that were definitely positive or with one definitely positive and the other doubtful were considered sensitized. Ten of 35 new beekeepers (28.6%) and 3 of 36 controls (8.3%) developed sensitivity to Hb venom during the 5-year period. The risk ratio in incidence studies was calculated at 3.43 (SE of log risk ratio = 0.61; 95% CI of risk ratio = 1.03-11.42). All sensitized beekeepers were detected within the first 18 months of occupational exposure; 8 of 10 (80%) beekeepers were detected during the initial 12 months and the 2 remaining beekeepers were detected between 12 and 18 months. One of 35 (2.9%) beekeepers and 1 of 36 controls (2.8%) were sensitized to Cw venom. The number of stings per year and atopy had no effect on sensitization rate. Although predisposing factors to sensitization or anaphylaxis could not be identified, beekeepers developed sensitization to bee venom in <18 months.

Adult↗

Penicillin hypersensitivity: value of clinical history and skin testing in daily practice.

Penicillin often is excluded as a treatment option based on patients' self-reported history of an adverse reaction to penicillin. The objective of this prospective study was to determine the likelihood of true penicillin allergy in patients with vague and convincing histories of penicillin allergy and to evaluate the diagnostic value added by appropriate skin testing. Six hundred thirty-eight patients with prior beta-lactam intake had a current indication for penicillin therapy and were referred for testing with the major (benzylpenicilloyl polylysine) and minor (minor determinant mixture) penicillin determinants from the inpatient and outpatient service of Athens University Dermatological hospital from January 2000 to December 2002. The prevalence of positive skin tests in the total group and in those patients with vague and convincing histories of penicillin allergy was determined. Positive skin tests were observed in 19/638 (3%) of the total group, 5 out of 542 (0.9%) patients without any history of penicillin allergy, 14 out of 96 (14.6%) patients with vague history (confidence interval [CI] 95% = 5.95-59.92), and 13 out of 18 (72.2%) patients with a convincing history of type I hypersensitivity reaction (chi2 = 286.3: odds ratio = 281.3: CI 95% = 62.19-1440.8). Patients with a vague history of penicillin allergy are 18 times more likely to have a positive penicillin skin test, and a convincing reaction history increases the likelihood by 281-fold compared with patients without a history of penicillin allergy. However, the fact that 5 of 18 (27.8%) patients with a convincing history were negative when skin tested points out that skin testing is helpful if the need for penicillin administration is compelling.

Adolescent↗