An intramolecular disulphide bond in human 4E-T affects its binding to eIF4E1a protein.

The cap at the 5'terminus of mRNA is a key determinant of gene expression in eukaryotic cells, which among others is required for cap dependent translation and protects mRNA from degradation. These properties of cap are mediated by several proteins. One of them is 4E-Transporter (4E-T), which plays an important role in translational repression, mRNA decay and P-bodies formation. 4E-T is also one of several proteins that interact with eukaryotic initiation factor 4E (eIF4E), a cap binding protein which is a key component of the translation initiation machinery. The molecular mechanisms underlying the interactions of these two proteins are crucial for mRNA processing. Studying the interactions between human eIF4E1a and the N-terminal fragment of 4E-T that possesses unstructured 4E-binding motifs under non-reducing conditions, we observed that 4E-T preferentially forms an intramolecular disulphide bond. This "disulphide loop" reduces affinity of 4E-T for eIF4E1a by about 300-fold. Considering that only human 4E-T possesses two cysteines located between the 4E binding motifs, we proposed that the disulphide bond may act as a switch to regulate interactions between the two proteins.

Tetralogia de Fallot Associada a Artéria Subclávia Direita Aberrante. Implicações Clínicas / Tetralogy of Fallot Associated with Aberrant Right Subclavian Artery. Clinical Implications

Resumo Desde a primeira descrição da tetralogia de Fallot (ToF) em 1671 por Niels Stensen e em 1888 por Étienne-Louis Arthur Fallot, vários trabalhos relataram essa anomalia juntamente com suas variantes e anomalias cardiovasculares concomitantes. A artéria subclávia direita aberrante (ASDA) é a anomalia do arco aórtico mais comum. Diferentemente da artéria subclávia esquerda aberrante, a ocorrência de ASDA em pacientes com ToF só foi relatada casuisticamente. Apresentamos dois pacientes de ToF com ASDA. É importante notar que o conhecimento da coexistência das duas anomalias tem pontos muito práticos durante correções endovasculares ou cirúrgicas de defeitos cardíacos congênitos (inclusive ToF).

Abstract Since the first description of Tetralogy of Fallot (ToF) in 1671 by Niels Stensen and in 1888 by Étienne-Louis Arthur Fallot, numerous papers have reported on this anomaly, along with its variants and concomitant cardiovascular anomalies. Aberrant right subclavian artery (ARSA) is the most common anomaly of the aortic arch. Different from the left aberrant subclavian artery, occurrence of ARSA in ToF-patients has only casuistically been reported so far. The present study reports on two ToF-patients with ARSA. It is important to note that knowledge of the coexistence of both anomalies has highly practical points during surgical or endovascular corrections of congenital heart defects (including ToF).

Hierarchical approach for the rational construction of helix-containing nanofibrils using α,ß-peptides.

The rational design of novel self-assembled nanomaterials based on peptides remains a great challenge in modern chemistry. A hierarchical approach for the construction of nanofibrils based on α,ß-peptide foldamers is proposed. The incorporation of a helix-promoting trans-(1S,2S)-2-aminocyclopentanecarboxylic acid residue in the outer positions of the model coiled-coil peptide led to its increased conformational stability, which was established consistently by the results of CD, NMR and FT-IR spectroscopy. The designed oligomerization state in the solution of the studied peptides was confirmed using analytical ultracentrifugation. Moreover, the cyclopentane side chain allowed additional interactions between coiled-coil-like structures to direct the self-assembly process towards the formation of well-defined nanofibrils, as observed using AFM and TEM techniques.

Characterization of the molecular chaperone ClpB from the pathogenic spirochaete Leptospira interrogans.

Leptospira interrogans is a spirochaete responsible for leptospirosis in mammals. The molecular mechanisms of the Leptospira virulence remain mostly unknown. Recently, it has been demonstrated that an AAA+ chaperone ClpB (a member of the Hsp100 family) from L. interrogans (ClpBLi) is not only essential for survival of Leptospira under the thermal and oxidative stresses, but also during infection of a host. The aim of this study was to provide further insight into the role of ClpB in the pathogenic spirochaetes and explore its biochemical properties. We found that a non-hydrolysable ATP analogue, ATPγS, but not AMP-PNP induces the formation of ClpBLi hexamers and stabilizes the associated form of the chaperone. ADP also induces structural changes in ClpBLi and promotes its self-assembly, but does not produce full association into the hexamers. We also demonstrated that ClpBLi exhibits a weak ATPase activity that is stimulated by κ-casein and poly-lysine, and may mediate protein disaggregation independently from the DnaK chaperone system. Unexpectedly, the presence of E. coli DnaK/DnaJ/GrpE did not significantly affect the disaggregation activity of ClpBLi and ClpBLi did not substitute for the ClpBEc function in the clpB-null E. coli strain. This result underscores the species-specificity of the ClpB cooperation with the co-chaperones and is most likely due to a loss of interactions between the ClpBLi middle domain and the E. coli DnaK. We also found that ClpBLi interacts more efficiently with the aggregated G6PDH in the presence of ATPγS rather than ATP. Our results indicate that ClpB's importance during infection might be due to its role as a molecular chaperone involved in reactivation of protein aggregates.

[Autoimmune polyglandular syndromes - literature review and analysis of clinical course in chosen cases]. / Zespoly autoimmunologicznych zaburzen wielogruczolowych - przeglad pismiennictwa oraz analiza przebiegu choroby u wybranych przypadków.

Autoimmune polyglandular syndromes (APS) are the conditions characterized by coexistence of at least two organ-specific endocrine autoimmune disorders. The syndromes often coexist with connective tissue diseases with the presence non-organ specific antibodies. The aim of the study was to present two clinical cases of polymyositis and dermatomyositis in the course of APS type 3d. Case 1, a 24-year-old woman, with diabetes mellitus type 1 was diagnosed at the age of 17 years and polymyositis recognized at the age of 24 years based on clinical manifestations and additional tests (proximal muscle weakness, typical electromyographic changes, typical histopathological changes in skin and muscles biopsy, elevated muscle enzymes) accompanied by interstitial lung disorder. Moreover, Hashimoto`s autoimmune thyroiditis was diagnosed. Case 2, a 47-year-old man, with a several-year history of diabetes mellitus type 1, diagnosed with dermatomyositis and autoimmune thyroiditis. The immunosuppressive therapy was instituted in both cases, which reduced the symptoms of connective tissue disease. To sum up, about 25-30% of patients are affected by extraglandular autoimmune diseases, including connective tissue diseases, in the course of APS. An interdisciplinary approach is required in this group of conditions due to a multitude of disorders as well as diagnostic and therapeutic difficulties.

Catheter ablation of complex left atrial arrhythmias in patients after percutaneous or surgical mitral valve procedures.

BACKGROUND: Mitral valve defects are frequently associated with atrial arrhythmias. Percutaneous or surgical mitral valveprocedures may reverse adverse haemodynamic consequences of the valvular defect but have little effect on the arrhythmiaitself. With safety concerns and few outcome data, the role of catheter ablation in these patients has not been established yet. AIM: To assess safety and efficacy of catheter ablation of complex left atrial arrhythmias in patients after percutaneous orsurgical mitral valve procedures. METHODS: We studied 14 patients (mean age 55 ± 11 years; 9 females) with a history of percutaneous mitral commissurotomy (PMC; n = 5), surgical valvuloplasty (n = 3), or mitral valve replacement (n = 6) due to mitral stenosis (MS; n = 8) or mitral regurgitation (MR; n = 6). In surgically treated patients, concomitant pulmonary vein isolation was performed in 6 patients and tricuspid valvuloplasty in 4 patients. Atrial fibrillation (AF) was the only arrhythmia in 7 patients, including all 5 patients after PMC (paroxysmal AF in 2 patients, persistent AF in 4 patients, long-persistent AF in 1 patient). Left atrial tachycardia (AT) was the prevailing arrhythmia in 7 of 9 patients after surgical procedures (median of 2 morphologies per patient), lasting uninterrupted for 1 to 48 months before the ablation procedure. The ablation scheme was adjusted to the clinical and electrophysiological status and included pulmonary vein isolation, linear lesions and ablation of fragmented potentials. Atrial tachycardias were mapped and ablated using activation and entrainment mapping. RESULTS: Efficacy of ablation after a single procedure was 36%. A total of 25 ablations were ultimately performed in the study group. During 23 ± 13 months of follow-up, stable sinus rhythm (SR) was present in 10 (71.4%) patients, including 4 on antiarrhythmic drugs. No differences in the efficacy of ablation were seen between patients with MS and MR, with SR obtained in5 of 8 patients and 5 of 6 patients, respectively (p = 0.57). Similarly, no differences in regard to SR maintenance were noted between patients previously treated by a percutaneous or surgical procedure (percutaneous treatment: SR in 3 of 5 patients; surgical treatment: SR in 7 of 9 patients, p = 0.58). SR was obtained in 5 of 7 patients in whom the original arrhythmia was AF and in 5 of 7 patients who had AT (p = 1.00). Patients in whom stable SR was obtained showed a significantly better functional status as assessed by the New York Heart Association classification, accompanied by a reduction of the left atrial dimension and an increase in the left ventricular ejection fraction. CONCLUSIONS: Catheter ablation of complex left atrial arrhythmias in patients after percutaneous or surgical mitral valve proceduresis an effective and safe therapeutic option. Recurrences after the first ablation are frequent and patients may require repeat ablations. Achieving stable SR significantly reduces complaints related to the arrhythmia and improves patient clinical status.

Catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: atrial fibrillation type determines the success rate.

BACKGROUND: Atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) is generally associated with deterioration of the clinical status, functional capacity, and quality of life. It is also an independent risk factor for stroke and death. Studies evaluating the effectiveness of AF ablation in this cohort are relatively scant, have included relatively few patients, and their results are somewhat conflicting. Thus, the aim of this study was to assess the safety and efficacy of catheter ablation of AF in patients with HCM. METHODS: Thirty patients (10 females; mean age 48.7 ± 11 years) with drug-refractory paroxysmal (n = 14), persistent (n = 7), or long-persistent (> 1 year; n = 9) AF were prospectively recruited into the study. Eleven patients were in New York Heart Association (NYHA) class I, 13 patients were in NYHA class II, and 6 patients were in NYHA class III. Mean atrial volume was 180 ± 47 mL, interventricular septum thickness was 20.5 ± 6.3 mm, and left atrial area was 29.8 ± 6.2 cm2. Ablation protocol was adjusted to the clinical and electrophysiological status of the patients. Pulmonary vein isolation and bidirectional cavo-tricuspid isthmus block were performed in all patients. In addition, left atrial linear lesions were created and complex fragmented atrial potentials were ablated in patients with persistent and long-persistent AF, as well as during repeated procedures. RESULTS: At 12 months, stable sinus rhythm (SR) was present in 16 (53%) patients, significantly more frequently in patients with paroxysmal AF (71% in SR) compared to those with persistent (57.1% in SR) or long-persistent (22% in SR) AF. A significant reduction of AF burden was observed in 85.7% of patients with paroxysmal AF, 71.4% of patients with persistent AF, and 55.5% of patients with long-persistent AF. Single procedure success rate was 33% (10 patients), and repeat ablation procedures were performed in 13 patients. No periprocedural complications occurred. Thromboembolic events were noted in 2 patients with arrhythmia recurrence during the follow-up, including stroke in 1 patient and peripheral embolism in the other patient. In both these patients, heart failure worsening was observed during these events, and anticoagulation was inadequate in one of them. Five of 16 patients in whom stable SR was observed during the follow-up were off antiarrhythmic drug therapy at final evaluation. In the other 6 patients, antiarrhythmic drug therapy was continued due to ventricular arrhythmias. Successfully treated patients more often had paroxysmal AF (successful ablation: paroxysmal AF in 10 of 16 patients; unsuccessful ablation: paroxysmal AF in 4 of 14 patients; p = 0.009) and were younger (45 ± 11.5 years vs. 52.6 ± 9.2 years; p = 0.046). In addition, a trend toward a reduced need for cardioversion at the end of the procedure was also observed in these patients (3 patients in the successful ablation group vs. 8 patients in the unsuccessful ablation group; p = 0.056). In multivariate regression analysis, paroxysmal AF was the only independent predictor of a successful outcome. CONCLUSIONS: Catheter ablation of AF in patients with HCM is an effective and safe therapeutic option, particularly in patients with paroxysmal AF. Effectiveness of ablation is significantly smaller in patients with persistent AF and even more so in those with long-persistent AF. Repeated procedures were often necessary. Continued antiarrhythmic drug therapy is often required due to a significant degree of atrial remodelling.

Geohelminth egg contamination of children's play areas in the city of Lodz (Poland).

The contamination of soil and sand with helminth eggs in children's play areas in Lodz (Poland) was assessed over two seasons using the flotation method with saturated sodium nitrate solution. A total of 88 samples were examined from 7 children's playgrounds from various public parks, 6 sandpits situated in school or kindergarten areas and 9 school sports fields. The differences in the number of positive samples from these sites were significant (χ(2)=21.83, d.f.=2 and p<0.0001). The highest rate of contamination was found in the area around sports fields. (15.7%). There was a significant difference between the frequencies of positive samples from the surface and from the deeper layers of the examined sites (χ(2)=11.41, d.f.=1, and p=0.0007). The average density of geohelminth eggs in 100g of soil or sand was 1.1 from sports fields, 0.4 from playgrounds and 0.07 from fenced sandpits. Throughout the study, 4 genera of nematode eggs (Toxocara, Uncinaria/Ancylostoma, Ascaris, Trichuris) and 1 genus (Cystoisospora spp.) of oocysts were detected. A total of 62 eggs were recovered, and 43.5% were fully developed to embryonated egg stages. The contamination rate was different in autumn 2010 and spring 2011, but there was no significant difference in the number of positive findings between these seasons. The helminth eggs were found in 10.9% and 7.6% of samples collected in the spring and in the autumn, respectively. The most frequently seen eggs were from Toxocara sp., which were the most prevalent in both seasons.

The role of B-type natriuretic peptide in the evaluation of left atrioventricular valve regurgitation following surgical repair of partial atrioventricular canal.

BACKGROUND: Left atrioventricular valve (LAVV) regurgitation usually follows surgical repair of partial atrioventricular canal (PAVC). Although measurements of B-type natriuretic peptide (BNP) levels are useful for the monitoring and prediction of outcomes in chronic mitral regurgitation, no data are available on the role of BNP measurements in the assessment of LAVV regurgitation in patients after surgical correction of PAVC. AIM: To determine the role of plasma BNP determination in the assessment of LAVV regurgitation in patients after surgical repair of PAVC. METHODS: We evaluated 41 patients who had undergone surgery for PAVC between 1968 and 2005 with preserved left ventricular ejection fraction (LVEF, mean age at follow-up: 39.2 ± 14.0 years, mean age at the time of surgery: 31.3 ± 15.6 years, 32 females) and 13 healthy controls (mean age: 38.9 ± 13.2 years, 9 females). All the subjects had undergone transthoracic echocardiography and had their plasma BNP levels determined. LAVV regurgitation was assessed qualitatively on 1+ to 4+ grading scale and quantitatively by calculating the effective regurgitant orifice area (EROA). RESULTS: LAVV regurgitation was present in 40 (97.6%) patients. Compared to patients with mild-to-moderate LAVV regurgitation (grade 1+ to 2+/EROA 〈 0.4 cm²) evaluated qualitatively and quantitatively, the group with severe regurgitation (grade 3+ to 4+/EROA ≥ 0.4 cm²) had higher values of left atrial volume (LAvol) and right ventricular (RV) systolic pressure, although there was no significant difference in plasma BNP levels. There were significant correlations between BNP levels and LAvol (r = 0.54, p = 0.0001), age at follow-up (r = 0.61, p=0.0001), age at the time of surgery (r = 0.58, p = 0.0001), RV diastolic diameter (r = 0.38, p = 0.02) and RV systolic pressure (r = 0.48, p = 0.002). Multivariate logistic regression analysis showed that only LAvol and age at the time of surgery but not the degree of LAVV regurgitation were independently associated with elevated plasma BNP levels. CONCLUSIONS: In patients late after surgical repair of the PAVC with preserved LVEF, plasma BNP levels reflect the consequences of the shunt at atrial level and LAVV regurgitation expressed by LAvol but it does not allow to estimate the severity of regurgitation.

Current problems concerning parasitology and mycology with regard to diseases of the skin and its appendages.

Current issues concerning Parasitology and Mycology with regard to diseases of the skin and its appendages are presented. Aspects of diagnostics, clinical picture and therapy of skin and nail mycoses, as well as difficulties in the diagnosis and treatment of both native parasitoses (toxoplasmosis) and imported human tropical parasitoses (malaria, filariosis) have been emphasised. The clinical importance of environmental mould fungi in nosocomial infections and fungal meningitis, as well as selected properties of fungi isolated from patients with head and neck neoplasms treated by radiotherapy are discussed. Other mycological topics include the characteristics of newly-synthesized thiosemicarbazides and thiadiazoles as potential drugs against toxoplasmosis and their biological activity against Toxoplasma gondii tachyzoites, selected molecular mechanisms of resistance to azoles, Candida albicans strains and a new tool (barcoding DNA) for describing the biodiversity of potential allergenic molds. The importance of environmental factors in pathogenesis of mycoses and parasitoses is noted. The characteristics of pathogenic fungi isolated from natural ponds in Bialystok and potentially pathogenic yeast-like fungi isolated from children's recreation areas in Lodz are presented. The ongoing problem of anthropozoonoses is considered, as are the roles of stray cats and dogs in contaminating soil with the developing forms of intestinal parasites. The characteristics of the human microbiome, including population composition, activity and their importance in normal human physiology, are presented, as are the major goals of the Human Microbiome Project initiated by National Institutes of Health (NIH).

[Signs of retinoblastoma]. / Objawy siatkówczaka.

PURPOSE: Retrospective analysis of retinoblastoma symptoms in patients treated in Ophthalmological Clinic in Krakow. MATERIAL AND METHODS: A retrospective chart review was conducted of 293 retinoblastoma patients from our center (1969-2008). RESULTS: A total of 170 (58%) of 293 patients presented with leukocoria, 81 (27.6%) patients had strabismus, 22 (7.5%) had atypical sings, 12 (4.1%) was detected by chance. Eight (2.8%) patients who had a family history of retinoblastoma and were clinically screened for retinal tumors from birth were diagnosed younger. CONCLUSIONS: We recommend routine dilated fundoscopic examination by an ophthalmologist for early detection of retinoblastoma before leukocoria and strabismus.

Cell motility affects the intensity of gap junctional coupling in prostate carcinoma and melanoma cell populations.

Connexins and gap junctions play a crucial role during carcinogenesis. While diverse regulatory systems have been shown to modulate their function, the influence of cell motility on the intensity of gap junctional intercellular coupling has yet to be systematically addressed. Since cancer cell motility and intercellular coupling determine cancer development, we aimed at elucidating how mutual cell translocation modulates the intensity of gap junctional coupling in cell populations. Time-lapse analyses of the motility of connexin43 (Cx43)-coupled rat prostate carcinoma (MAT-LyLu) and mouse melanoma (B16) cells cultured on hyper-adhesive substrata revealed a reduced intensity of intercellular translocations in the two cell populations compared to the control conditions. While no detectable effects on the architecture of the actin cytoskeleton and Cx43 expression and phosphorylation were observed, the inhibition of cell motility was paralleled by an increase in the abundance of Cx43-positive plaques in cell-to-cell contacts and an enhancement of gap junctional coupling in cell populations cultured on hyper-adhesive substrata. Thus, a direct correlation between two cellular parameters crucial for carcinogenesis, i.e. cell motility and gap junctional coupling intensity exists in cancer cell populations.

[The analysis of refractive error in children and adolescents from 6-15 years of age based on 1000 examinations in two major Polish regions]. / Ocena refrakcji u dzieci i mlodziezy w wieku od 6 do 15 lat na podstawie badan 10000 osób, przeprowadzonych w województwach mazowieckim i dolnoslaskim.

PURPOSE: The aim of this study is to present the results of screening examinations of refractive errors, taken on 1002 of school children ranging from 6 to 15 years of age. MATERIAL AND METHODS: As the result of Internet screening visual acuity and color perception tests named "I can see..." in 10,021 children from randomly chosen schools in Poland in the year 2002, the group of 1002 children was chosen. In this group, the subjective and objective refractive error examination was taken as well as the visual acuity test, color perception with the use of Ishihara tables and full ophthalmologic examination. RESULTS: Average visual acuity was RE: 0.72 (SD +/- 0.31) and LE: 0.72 (SD +/- 0.31). The prevalence of emmetropia was 34%. In the examined group myopia in 17%, hyperopia in 20%, astigmatism in 5.5% of children was found, and in 24.5% of patients complex errors occur such as myopic and hyperopic astigmatism.

[Lipomatous hyperthrophy of the atrial septum - two case reports]. / Tluszczowy przerost przegrody miedzyprzedsionkowej.

Lipomatous hyperthrophy of the atrial septum is a rarely diagnosed but not rarely occurring benign hyperplasia of the lipomatous tissue. Apart from possible arrhythmias and single description of superior vena cava obstruction by extremely hypertrophied septum, lipomatous hyperthrophy does not seem to have any significant clinical importance. The potential danger is however associated with a false diagnosis of malignant tumor of the heart and unnecessary selection for cardiac surgery. We present two patients with the final diagnosis of benign lipomatous hyperthrophy of the atrial septum, referred to our center with an initial diagnosis of right atrial tumor.