Polymorphisms of the CD14 gene and atopic phenotypes in Czech patients with IgE-mediated allergy

IgE-mediated allergy is a common chronic disorder resulting from interactions between genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localised on chromosome 5q31.1, a region linked to asthma and bronchial hyperresponsiveness. We investigated the relationship among atopic phenotypes and six polymorphisms in the CD14 gene. Polymerase chain reaction with RFLP analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n=282) and random controls (n=187). No significant differences in allele or genotype frequencies for individual polymorphisms between patients and controls were found. However, when atopic patients were subdivided into subjects with positive and with negative skin prick tests for separate antigens, T allele of the 1341G/T polymorphism was significantly associated with positive reactivity to mites (P=0.007) and moulds (P=0.041). Similarly, the C allele frequency of the −159C/T variant was increased in patients with positive skin prick tests for mites (P=0.046) and moulds (P=0.056). In haplotype analysis, the common −1619A/−1359G/−550C/−159C/+1188G/+1341T haplotype was associated with positive reaction to these antigens (P values: 0.0008–0.0035). Our study supports the idea that CD14 plays a role in IgE-mediated allergic diseases, and its gene polymorphisms can be important for manifestation of these disorders.     

The effect of down-regulation of mitochondrial RNA-binding proteins MRP1 and MRP2 on respiratory complexes in procyclic Trypanosoma brucei

MRP1 and MRP2 are multifunctional mitochondrial RNA-binding proteins with a regulatory role in RNA editing and putative role(s) in RNA processing in Trypanosoma brucei. Silencing of MRP1 and/or MRP2 by RNA interference affected the assembly and functionality of respiratory complexes. The absence of several subunits of complexes I, III and IV resulted in their disintegration and subsequent decrease of specific activities and also caused a significant decrease of membrane potential. The overall respiration in the interfered cells decreased by only about 20%, since the trypanosome alternative oxidase effectively replaced the missing cytochromes and became the principal terminal oxidase.     

Analysis of ERBB2 and TOP2A gene status using fluorescence in situ hybridization versus immunohistochemistry in localized breast cancer

The aim of our study was to assess the ERBB2 and TOP2A gene status in breast carcinoma tissue using fluorescence in situ hybridization (FISH) and to compare their amplification with immunohistochemistry assay (IHC) of the ERBB2, resp. topoisomerase IIalpha proteins. TOP2A status is important in tailored treatment as topoisomerase IIalpha is the molecular target for topoisomerase IIalpha inhibitors. This study was conducted to determine whether the methods are equivalent in their assessment of TOP2A status and to correlate the genetic findings with basic tumor and disease characteristics. Locus specific ERBB2, TOP2A genes and chromosome 17 centromeres (CEP17) probes were hybridized to 72 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with non-metastatic breast carcinoma (M0). The ERBB2, TOP2A and CEP17 signals were counted and gene numbers per nucleus or per CEP17 were calculated, respectively. Sections were also stained with commercial polyclonal antibody (HercepTestTM), anti-topoisomerase IIalpha monoclonal antibody (clone SWT3D1) and scored for the presence of membrane/nuclear staining. ERBB2 amplification was found in 20.3%, ERBB2 and TOP2A co-amplification was detected in 14.5% of cases. Deletion of the ERBB2/TOP2A gene was found in 1.4/2.8% of sections, respectively. Concordance of FISH and IHC techniques in the evaluation of ERBB2 and TOP2A status was found in 88.4% and 66.7%, respectively. The low concordance of FISH versus IHC in the evaluation of TOP2A status was mainly due to the presence of TOP2A amplified tumors in IHC negative or weakly positive specimens. Topoisomerase IIalpha expression was increased in bigger tumors, although direct correlation with tumor grading was not found. ERBB2 amplification was found in more aggressive breast cancers with grades 2 and 3, respectively. Interestingly, chromosome 17 polysomy was more frequently observed among older women (>55 years), suffering usually from less aggressive disease. Our results confirm the high concordance of the ERBB2 and TOP2A gene co-amplification in breast carcinoma. Differences between FISH and IHC in the case of ERBB2 gene status were found only in IHC 2+ sections as reported in the literature. However, our study points to the importance of FISH examination of TOP2A gene status in all tumors with ERBB2 amplification.     

New possibilities of making the diagnosis of Caplan syndrome

We describe a 56-year old man with rheumatoid arthritis and pulmonary nodules detected by HRCT. Needle biopsy confirmed the diagnosis of Caplan syndrome.     

Prevention of venous thromboembolism in psychiatry

The hospitalized patients of the psychiatric wards represent a risk group for the development of venous thromboembolism. Apart from sedative administration, total movement reduction, bad life style and daily routine and increased body weight, there is negative impact of dehydration, prolonged hospitalization and sometimes immobilisation in consequence of mechanical restraints. A large amount of patients are treated with antipsychotics that have a series of adverse effects. Depending of the drug used, the most frequent of them are somnolence, fatigue, extrapyramidal syndrome, hypotension, hepatotoxicity, increased body weight, prolongation of the QT interval of the ECG with a risk of ventricular arrhythmias, hematopoietic disorders, lipid or glycide metabolism disorders or hyperprolactinemia. Another potential adverse effect of these drugs is the heightened risk of venous thromboembolism development (deep vein thrombosis and/or pulmonary embolism). There is the risk of a pathological blood clotting event in psychiatric patients, especially those treated with antipsychotics. Although it is not high, it can have fatal consequences when combined with a relatively frequent pulmonary embolism and difficult diagnostics of thromboembolism. An algorithm for thromboembolism prevention has been developed. It involves important general risk factors of venous thrombosis (VTE history, immobilisation, malignancy, age over 75 years etc.) and also markers (physical restraints, dehydration, obesity, antipsychotics use) that can participate in the pathogenesis of venous thrombosis in the hospitalized psychiatric patients with limited motility. The authors believe that this prophylaxis is indicated, safe, effective and that it improves the quality of life at relatively low costs.     

Primary aldosteronism in gravidity

Endocrinology and obstetrics have one thing in common--diagnosis and treatment endocrine diseases in gravidity. These are modified by physiological changes in gravidity, often missing data and tests in normal condition and the influence of diagnosis and treatment on the pregnant female and fetus have also to be taken into consideration. If diagnosis of primary aldosteronism is suspected, suprimed plasmatic renin activity is determinant indicator (disregarding arterial hypertension, hypokaliaemia, hyperkaliuresis and proteinuria) as well as ultrasound diagnostics or adrenal gland diagnostics means magnetic resonance imaging. Aldosteron produced adenomas may by treated by adrenalectomy in the second trimester, late diagnosed adenoma and hyperplastic forms are treated by the administration of the respective medicaments.     

Thyroid carcinomas and Hirschsprung's disease--10-year experience with molecular genetic testing of the RET proto-oncogene

In the last ten years, research has confirmed the role of the RET proto-oncogene in the pathogenesis of thyroid cancer such as medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC), multiple endocrine neoplasia type 2 (MEN 2) and Hirschsprung's disease that can be associated with MTC or MEN 2. Through the use of molecular genetic testing, we are able to detect gene mutations and the course the disease might take can be predicted, thus enabling us to cure mutation carriers among the high-risk patients can at a very early, clinically asymptomatic stage of the disease; prophylactic total thyreoidectomy in said patients is recommended. At this juncture, there is extensive on-going research on the physiological role played by the RET proto-oncogene on the normal proliferation, differentiation and survival of the cell. Thanks to the new findings there are now possibilities of the theurapeutic use of gene therapy on an RET signaling cascade level in near future.