10 research outputs found
Chronic granulomatous disease: the European experience.
CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a "respiratory burst", essential for the clearance of phagocytosed micro-organisms. CGD patients lack this mechanism, which leads to life-threatening infections and granuloma formation. However, a clear picture of the clinical course of CGD is hampered by its low prevalence (approximately 1:250,000). Therefore, extensive clinical data from 429 European patients were collected and analyzed. Of these patients 351 were males and 78 were females. X-linked (XL) CGD (gp91(phox) deficient) accounted for 67% of the cases, autosomal recessive (AR) inheritance for 33%. AR-CGD was diagnosed later in life, and the mean survival time was significantly better in AR patients (49.6 years) than in XL CGD (37.8 years), suggesting a milder disease course in AR patients. The disease manifested itself most frequently in the lungs (66% of patients), skin (53%), lymph nodes (50%), gastrointestinal tract (48%) and liver (32%). The most frequently cultured micro-organisms per episode were Staphylococcus aureus (30%), Aspergillus spp. (26%), and Salmonella spp. (16%). Surprisingly, Pseudomonas spp. (2%) and Burkholderia cepacia (<1%) were found only sporadically. Lesions induced by inoculation with BCG occurred in 8% of the patients. Only 71% of the patients received antibiotic maintenance therapy, and 53% antifungal prophylaxis. 33% were treated with gamma-interferon. 24 patients (6%) had received a stem cell transplantation. The most prominent reason of death was pneumonia and pulmonary abscess (18/84 cases), septicemia (16/84) and brain abscess (4/84). These data provide further insight in the clinical course of CGD in Europe and hopefully can help to increase awareness and optimize the treatment of these patients
Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma
Papillary thyroid carcinoma (PTC) exhibits various molecular abnormalities, both
when sporadic and radiation-related. PTC is still diagnosed in adult individuals who
were younger than 18 years at the time of the Chornobyl accident in 1986 and lived
within the contaminated area. The preoperative diagnosis of PTC is based on
ultrasound-guided fine needle aspiration cytology (FNAC), which is highly informative
in up to 90% of biopsies. FNAC is not informative for the discrimination of follicular
thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). Moreover, FNAC is
often unreliable for diagnosis of cystic PTC due to its common presentation as a mural
nodule in a cystic mass. In case of cystic PTC, biopsy sometimes reveals a cystic fluid
containing insufficient amount of representative cells for cytology.
In this work, PTC was characterized in relation to irradiation from radioactivity at
childhood. Possible preoperative diagnostic markers for discrimination between PTC
and other follicular thyroid neoplasms were identified, and their validity was tested.
In Study I molecular, genetic and clinical characteristics in 70 post-Chornobyl
PTCs were investigated. A common BRAF 1799T>A mutation was detected in 26 cases,
overrepresentation of RET/PTC1 in 20 whereas RET/PTC3 was found in 4 cases. BRAF
mutation was observed 3.5 times less frequent in the PTC accompanied by chronic
lymphocytic thyroiditis (PTC/CLT) as compared to PTC only (12% vs. 44%). Greater
expression of cyclin A was observed in PTC ≥ 2 cm as compared to PTC < 2 cm (1.2%
vs. 0.6%). In conclusion, BRAF mutation and RET/PTC1 rearrangement as well as other
molecular features of adult post-Chornobyl PTC were partly overlapping with other
reported PTC cohorts.
In Study II the SELDI-TOF mass spectrometry method was applied for PTC, FTC,
FTA and normal thyroid tissue (NT). Significant overexpression of the protein S100A6
was identified in PTC as compared to FTC, FTA and NT (p < 0.05). This result was
verified both by Western blot (WB), using the same samples, and by IHC in these and
additionally in the PTC samples investigated in Study I. Moreover, the presence of two
post-translational modifications of S100A6 was observed and verified by LC-MS/MS.
S100A6 expression is strongly associated with PTC, and can therefore be tested for
discrimination between follicular thyroid tumors and PTC.
In Study III a two dimensional gel electrophoresis followed by MALDI-TOF mass
spectrometry for proteomic profiling of PTC, FTC and FTA was performed. 25 protein
spots showing significantly different expression between studied groups were identified.
Of these, 9 protein spots were selected for further analyses by WB using the initially
studied samples and by IHC using these as well as samples from Study I. The findings
suggest additional proteins to be deregulated in thyroid tumors, and their clinical
significance can now be further studied.
In Study IV preoperative diagnostic markers for PTC in cystic lesions were
identified by applying LC-MS/MS method. Out of all 1581 identified proteins, annexin
A3 (ANXA3), carboxymethylenebutenolidase homolog (CMBL) cytokeratin 19 (CK-
19) and S100A13 were selected for validation by IHC and WB. ANXA3 and CMBL
showed overexpression in both controls and PTCs, whereas S100A13 and CK-19 were
up-regulated in PTC only (p < 0.05), suggesting their possible role for discrimination
between cystic PTC and benign thyroid cysts