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1.
Int J Mol Sci ; 24(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37175920

RESUMO

Aberrant expression of glycans, i.e., oligosaccharide moiety covalently attached to proteins or lipids, is characteristic of various cancers, including urothelial ones. The binding of lectins to glycans is classified as molecular recognition, which makes lectins a strong tool for understanding their role in developing diseases. Here, we present a quantitative approach to tracing glycan-lectin interactions in cells, from the initial to the steady phase of adhesion. The cell adhesion was measured between urothelial cell lines (non-malignant HCV29 and carcinoma HT1376 and T24 cells) and lectin-coated surfaces. Depending on the timescale, single-cell force spectroscopy, and adhesion assays conducted in static and flow conditions were applied. The obtained results reveal that the adhesion of urothelial cells to two specific lectins, i.e., phytohemagglutinin-L and wheat germ agglutinin, was specific and selective. Thus, these lectins can be applied to selectively capture, identify, and differentiate between cancer types in a label-free manner. These results open up the possibility of designing lectin-based biosensors for diagnostic or prognostic purposes and developing strategies for drug delivery that could target cancer-associated glycans.


Assuntos
Lectinas , Neoplasias da Bexiga Urinária , Humanos , Lectinas/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Fito-Hemaglutininas/farmacologia , Aglutininas do Germe de Trigo , Polissacarídeos/metabolismo
2.
Neurol Neurochir Pol ; 57(6): 492-496, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38112647

RESUMO

AIM OF THE STUDY: To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP). CLINICAL RATIONALE FOR THE STUDY: Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications. MATERIAL AND METHODS: We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events. RESULTS: 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18-57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0-8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50-350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate.


Assuntos
Anticonvulsivantes , Convulsões , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada , Estudos Retrospectivos , Resultado do Tratamento
3.
Postepy Dermatol Alergol ; 39(6): 1134-1140, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36686011

RESUMO

Introduction: Cancers of the auricle and the external auditory canal (EAC) remain a relevant oncological problem. Aim: Presentation of the results after resections of conchal bowl and EAC carcinoma (with or without radical mastoid surgery) and after reconstructions (postauricular island flap - PIF). Material and methods: We analysed results of 37 patients with cancers of the auricular conchal bowl and EAC after tumour resection and reconstruction (2000-2017). Results: The cancers were completely excised in all patients, with no recurrences within at least 5 years after surgery. We noted venous congestion in 22 (59.4%) cases, pinning of the operated ear in 18 (48.6%), prominent earlobe in 14 (37.8%), and EAC constriction in 6 (16.2%) cases treated without radical mastoid surgery. Conclusions: Retroauricular approach in cancer of the auricular concha and EAC allowed for accurate evaluation of the tumour extent and proper surgical access, which facilitated complete removal of the tumour. Use of radical mastoid operation with conchal bowl resection and PIF reconstruction in patients with aquamous cell carcinoma or infiltrating basal cell carcinoma of auricular concha and osseous EAC resulted in cancer extirpation and good aesthetic outcomes, despite minor functional consequences. In these cancers mastoidectomy offered a wider access to determine the radicality of oncological resection.

4.
Postepy Dermatol Alergol ; 39(5): 980-985, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36457690

RESUMO

Introduction: Basal cell carcinoma (BCC) occurs in aggressive and non-aggressive forms. The expression of immunohistochemical markers varies in different types of BCC. Aim: Immunohistochemical analysis of selected proteins in BCCs. Material and methods: The immunohistochemical method was used to examine the immunoexpression of Bmi-1, CK15 and Bcl-2 in 56 cases of BCC divided into four groups. Results: Positive Bmi-1 staining 3-4+ level (nodular type) was seen in 91.3% of samples, 4+ (infiltrative) in 92.3%, 4+ (nodular/infiltrative) - 69.2%, 3+ - 30.8%, in BSC 3+ - 42.8%, and 28.6% each for 2+ and 4+. Low grade positivity (0-1+) in CK15 staining was present in 52.1% of nodular BCC, 46.2% - nodular/infiltrative, 92.3% - infiltrative, and 100% - BSC, but levels 2-3+ in nodular BCC in 47.8%, nodular/infiltrative BCC - 53.8%, infiltrative - 7.7%. Bcl-2 positivity (3-4+) was revealed in nodular BCC in 95.6%, (1-2+) in 100% of BSC, infiltrative and infiltrative/nodular BCC, but the lowest (0-1+) in 76.9% of nodular/infiltrative BCC, 71.4% of BSC, and in 38.4% of infiltrative BCC. Conclusions: Positive Bmi-1 staining was the highest in the aggressive infiltrative subtype of BCCs, whereas the lowest in basosquamous cell carcinomas (BSC). Infiltrative BCC was characterized by a lower level of CK15 expression than nodular BCC and nodular/infiltrative BCC. Differentiation of Bcl-2 expression depended on the type of tumour; the highest level was found in nodular BCC, low grade in nodular/infiltrative and infiltrative BCCs, and BSC.

5.
Mult Scler ; 27(6): 883-894, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32716690

RESUMO

BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment. OBJECTIVE: PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment. METHODS: Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc). RESULTS: Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL-W96), stabilizing above the lower limit of normal (baseline: 1.82 × 109/L; W48: 1.06 × 109/L; W96: 1.05 × 109/L). CD4 + and CD8 + T cells correlated highly with ALC from BL-W96 (p < 0.001). Relative to total T cells, naive CD4 + and CD8 + T cells increased, whereas CD4 + and CD8 + central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1-4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs. CONCLUSION: Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia. SUPPORT: Biogen.


Assuntos
Fumarato de Dimetilo , Esclerose Múltipla Recidivante-Remitente , Anti-Inflamatórios/uso terapêutico , Fumarato de Dimetilo/uso terapêutico , Humanos , Imunidade Humoral , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Prospectivos
6.
Catheter Cardiovasc Interv ; 98(3): 588-594, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33559279

RESUMO

OBJECTIVES: The present study was a prospective, single-center, single-arm study to investigate the efficacy of transcatheter pulmonary artery denervation (TPADN) in patients with combined postcapillary and precapillary PH (Cpc-PH) associated with left heart failure with reduced ejection fraction (HF-rEF). BACKGROUND: Pulmonary hypertension (PH) in patients with left ventricular systolic dysfunction has a negative impact on outcome. METHODS: The combination of pulmonary artery systolic pressure (PAPs) ≥60 mmHg, transpulmonary pressure gradient (TPG) ≥12 mmHg, nonreversible mean PAP, and pulmonary vascular resistance (PVR) ≥3.5 Wood Units was considered as too high risk for heart transplantation (HTx). The clinical efficacy endpoint was an improvement in 6-min walking test and the hemodynamic endpoints were changes in PAPs, PVR, and TPG between baseline and 6 months. Circumferential radiofrequency applications were delivered around distal main, left and right pulmonary arteries. At each ablation point temperature was 45°C and energy 10 W. RESULTS: TPADN was performed in 10 patients. At 6-month in 5 patients we observed reduction in PAP, PVR, TPG, and DPG and then 1 had successful HTx, 2 are on HTx waiting list, 2 received LVADs, 2 patients did not improve, and 3 patients died. CONCLUSIONS: TPADN may be beneficial in selected patients with HF-rEF and Cpc-PH.


Assuntos
Insuficiência Cardíaca , Hipertensão Pulmonar , Denervação , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Estudos Prospectivos , Volume Sistólico , Resultado do Tratamento , Resistência Vascular
7.
Eur Biophys J ; 49(6): 485-495, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32803311

RESUMO

The identification of cancer-related changes in cells and tissues based on the measurements of elastic properties using atomic force microscopy (AFM) seems to be approaching clinical application. Several limiting aspects have already been discussed; however, still, no data have shown how specific AFM probe geometries are related to the biomechanical evaluation of cancer cells. Here, we analyze and compare the nanomechanical results of mechanically homogenous polyacrylamide gels and heterogeneous bladder cancer cells measured using AFM probes of various tip geometry, including symmetric and non-symmetric pyramids and a sphere. Our observations show large modulus variability aligned with both types of AFM probes used and with the internal structure of the cells. Altogether, these results demonstrate that it is possible to differentiate between compliant and rigid samples of kPa elasticity; however, simultaneously, they highlight the strong need for standardized protocols for AFM-based elasticity measurements if applied in clinical practice including the use of a single type of AFM cantilever.


Assuntos
Hidrogéis/química , Microscopia de Força Atômica/métodos , Linhagem Celular , Módulo de Elasticidade , Humanos , Fenômenos Mecânicos
8.
Int J Mol Sci ; 21(22)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233645

RESUMO

Increasing attention is devoted to the use of nanomechanics as a marker of various pathologies. Atomic force microscopy (AFM) is one of the techniques that could be applied to quantify the nanomechanical properties of living cells with a high spatial resolution. Thus, AFM offers the possibility to trace changes in the reorganization of the cytoskeleton in living cells. Impairments in the structure, organization, and functioning of two main cytoskeletal components, namely, actin filaments and microtubules, cause severe effects, leading to cell death. That is why these cytoskeletal components are targets for antitumor therapy. This review intends to describe the gathered knowledge on the capability of AFM to trace the alterations in the nanomechanical properties of living cells induced by the action of antitumor drugs that could translate into their effectiveness.


Assuntos
Antineoplásicos/farmacologia , Citoesqueleto/efeitos dos fármacos , Microscopia de Força Atômica/métodos , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Citoesqueleto/patologia , Humanos , Neoplasias/tratamento farmacológico
9.
J Exp Bot ; 70(9): 2403-2418, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-30615184

RESUMO

A recent initiative named 'Crops in silico' proposes that multi-scale models 'have the potential to fill in missing mechanistic details and generate new hypotheses to prioritize directed engineering efforts' in plant science, particularly directed to crop species. To that end, the group called for 'a paradigm shift in plant modelling, from largely isolated efforts to a connected community'. 'Wet' (experimental) research has been especially productive in plant science, since the adoption of Arabidopsis thaliana as a laboratory model species allowed the emergence of an Arabidopsis research community. Parts of this community invested in 'dry' (theoretical) research, under the rubric of Systems Biology. Our past research combined concepts from Systems Biology and crop modelling. Here we outline the approaches that seem most relevant to connected, 'digital organism' initiatives. We illustrate the scale of experimental research required, by collecting the kinetic parameter values that are required for a quantitative, dynamic model of a gene regulatory network. By comparison with the Systems Biology Markup Language (SBML) community, we note computational resources and community structures that will help to realize the potential for plant Systems Biology to connect with a broader crop science community.


Assuntos
Produtos Agrícolas/fisiologia , Biologia de Sistemas/métodos , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/fisiologia , Cinética
10.
BMC Med Genet ; 19(1): 94, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29871609

RESUMO

BACKGROUND: Mutations of the SCN5A gene are reported in 2-4% of patients with dilated cardiomyopathy (DCM). In such cases, DCM is associated with different rhythm disturbances such as the multifocal ectopic Purkinje-related premature contractions and atrial fibrillation. Arrhythmia often occurs at a young age and is the first symptom of heart disease. CASE PRESENTATION: We present the case of 55-year old male with a 30-year history of heart failure (HF) in the course of familial DCM and complex ventricular tachyarrhythmias, which constituted 50-80% of the whole rhythm. The patient was qualified for heart transplantation because of the increasing symptoms of HF. We revealed the heterozygotic R222Q mutation in SCN5A by means of whole exome sequencing. After the quinidine treatment, a rapid and significant reduction of ventricular tachyarrhythmias and an improvement in the myocardial function were observed and this effect remained constant in the 2.5-year follow-up. This effect was observed even in the presence of concomitant coronary artery disease. CONCLUSIONS: Patients with familial DCM and Purkinje-related ventricular arrhythmias should be offered genetic screening. The quinidine treatment for the SCN5A R222Q mutation can be life saving for patients.


Assuntos
Antiarrítmicos/uso terapêutico , Cardiomiopatia Dilatada/genética , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Ramos Subendocárdicos/patologia , Quinidina/uso terapêutico , Taquicardia Ventricular/genética , Adulto , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/patologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Prognóstico , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/patologia , Adulto Jovem
11.
Pol J Pathol ; 67(3): 216-220, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28155969

RESUMO

The significance of the Quilty effect (QE) is not fully understood. It was once proposed to be related to acute cellular rejection (ACR). We aim to assess the relation between QE prevalence and antibody-mediated rejection (AMR). One thousand three hundred and fifty endomyocardial biopsies (EMBs) from 212 patients who underwent heart transplantation in the years 2001-2013 and survived a period of 30 days after the operation were diagnosed. In all EMBs routine HE staining and additional immunohistochemical staining with polyclonal antibody against C4d were performed. Microscopic findings were classified according to the new ISHLT 2013 criteria. Patients were separated into two groups: group 1 included those with at least one pAMR1 I+ and/or pAMR2 EMB (n = 16), and group 2 included the rest of the patients (n = 196). Presence of QE with distinguishing subtypes A and B (according to the first ISHLT 1990 criteria) was assessed. One hundred and twenty one EMBs from group 1 and 1229 EMBs from group 2 were diagnosed. Quilty effect type A was found in 16 (13.2%) EMBs in group 1 and in 96 (7.8%) EMBs in group 2, p < 0.001. Quilty effect type B was diagnosed in 52 (43%) EMBs in group 1 and in 245 (20%) EMBs in group 2, p < 0.001. The QE was not present in 53 (43.8%) EMBs in group 1 and in 888 (72.2%) EMBs in group 2, p < 0.001. The relation between QE prevalence and AMR is possible as the QE is present statistically more often in EMBs of patients with C4d capillary depositions.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Coração , Miocárdio/patologia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Humanos , Imuno-Histoquímica , Masculino , Prevalência
12.
Postepy Dermatol Alergol ; 33(1): 42-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26985178

RESUMO

INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm of the eyelids and surrounding structures, usually developing in the area of the lower lid and medial canthus. Invasive forms of BCC are connected with a high risk of recurrence, often due to incomplete excision of these lesions. AIM: Clinical and pathological analysis of recurrent BCCs of the eyelids and surrounding structures. MATERIAL AND METHODS: We present clinical and pathological analysis including immunohistochemical reaction to Ki-67 antigen of 19 patients (11 women, 8 men) operated for recurrent BCCs of the eyelids in 2000-2012. RESULTS: In most cases, recurrences were present on the lower lid and in the medial canthus. In 15 patients the histopathological type did not change and in 4 cases it transformed into more invasive forms. The values of Ki-67 index for primary BCCs ranged between 1% and 20%, and for relapsing lesions between 11% and 48%. CONCLUSIONS: Proper clinical and pathological evaluation to determine the risk of relapse in BCCs of the eyelids and surrounding structures should include the analysis of prognostic factors, in particular location and size, histopathological type and radicalness of surgical treatment of primary BCCs. Clinical and pathological analysis of patients with recurrent BCC of the eyelids and surrounding structures should be combined with the evaluation of proliferation index Ki-67, which is essential for prognosis and choice of the appropriate therapeutic method.

13.
BMC Med Genet ; 16: 21, 2015 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-25928149

RESUMO

BACKGROUND: In humans mutations in the PLN gene, encoding phospholamban - a regulator of sarcoplasmic reticulum calcium ATPase (SERCA), cause cardiomyopathy with prevalence depending on the population. Our purpose was to identify PLN mutations in Polish cardiomyopathy patients. METHODS: We studied 161 unrelated subjects referred for genetic testing for cardiomyopathies: 135 with dilated cardiomyopathy, 22 with hypertrophic cardiomyopathy and 4 with other cardiomyopathies. In 23 subjects multiple genes were sequenced by next generation sequencing and in all subjects PLN exons were analyzed by Sanger sequencing. Control group included 200 healthy subjects matched with patients for ethnicity, sex and age. Large deletions/insertions were screened by real time polymerase chain reaction. RESULTS: We detected three different heterozygous mutations in the PLN gene: a novel null c.9_10insA:(p.Val4Serfs*15) variant and two missense variants: c.25C > T:(p.Arg9Cys) and c.26G > T:(p.Arg9Leu). The (p.Val4Serfs*15) variant occurred in the patient with Wolff-Parkinson-White syndrome in whom the diagnosis of cardiomyopathy was not confirmed and his mother who had concentric left ventricular remodeling but normal left ventricular mass and function. We did not detect large deletions/insertions in PLN in cohort studied. CONCLUSIONS: In Poland, similar to most populations, PLN mutations rarely cause cardiomyopathy. The 9(th) PLN residue is apparently a mutation hot spot whereas a single dose of c.9_10insA, and likely other null PLN mutations, cause the disease only with low penetrance or are not pathogenic.


Assuntos
Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Cardiomiopatias/genética , Heterozigoto , Mutação , Penetrância , Adulto , Sequência de Aminoácidos , Sequência de Bases , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatias/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polônia
14.
J Acoust Soc Am ; 137(4): 1790-801, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25920832

RESUMO

This paper proposes and discusses an approach for the design and quality inspection of the morphology dedicated for sound absorbing foams, using a relatively simple technique for a random generation of periodic microstructures representative for open-cell foams with spherical pores. The design is controlled by a few parameters, namely, the total open porosity and the average pore size, as well as the standard deviation of pore size. These design parameters are set up exactly and independently, however, the setting of the standard deviation of pore sizes requires some number of pores in the representative volume element (RVE); this number is a procedure parameter. Another pore structure parameter which may be indirectly affected is the average size of windows linking the pores, however, it is in fact weakly controlled by the maximal pore-penetration factor, and moreover, it depends on the porosity and pore size. The proposed methodology for testing microstructure-designs of sound absorbing porous media applies the multi-scale modeling where some important transport parameters-responsible for sound propagation in a porous medium-are calculated from microstructure using the generated RVE, in order to estimate the sound velocity and absorption of such a designed material.

15.
J Acoust Soc Am ; 137(6): 3232-43, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26093413

RESUMO

This paper presents a methodology for the inverse characterization of sound absorbing rigid porous media, based on standard measurements of the surface acoustic impedance of a porous sample. The model parameters need to be normalized to have a robust identification procedure which fits the model-predicted impedance curves with the measured ones. Such a normalization provides a substitute set of dimensionless (normalized) parameters unambiguously related to the original model parameters. Moreover, two scaling frequencies are introduced, however, they are not additional parameters and for different, yet reasonable, assumptions of their values, the identification procedure should eventually lead to the same solution. The proposed identification technique uses measured and computed impedance curves for a porous sample not only in the standard configuration, that is, set to the rigid termination piston in an impedance tube, but also with air gaps of known thicknesses between the sample and the piston. Therefore, all necessary analytical formulas for sound propagation in double-layered media are provided. The methodology is illustrated by one numerical test and by two examples based on the experimental measurements of the acoustic impedance and absorption of porous ceramic samples of different thicknesses and a sample of polyurethane foam.

16.
J Transl Med ; 12: 192, 2014 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-25008357

RESUMO

BACKGROUND: BAG3 gene mutations have been recently implicated as a novel cause of dilated cardiomyopathy (DCM). Our aim was to evaluate the prevalence of BAG3 mutations in Polish patients with DCM and to search for genotype-phenotype correlations. METHODS: We studied 90 unrelated probands by direct sequencing of BAG3 exons and splice sites. Large deletions/insertions were screened for by quantitative real time polymerase chain reaction (qPCR). RESULTS: We found 5 different mutations in 6 probands and a total of 21 mutations among their relatives: the known p.Glu455Lys mutation (2 families), 4 novel mutations: p.Gln353ArgfsX10 (c.1055delC), p.Gly379AlafsX45 (c.1135delG), p.Tyr451X (c.1353C>A) and a large deletion of 17,990 bp removing BAG3 exons 3-4. Analysis of mutation positive relatives of the probands from this study pooled with those previously reported showed higher DCM prevalence among those with missense vs. truncating mutations (OR = 8.33, P = 0.0058) as well as a difference in age at disease onset between the former and the latter in Kaplan-Meier survival analysis (P = 0.006). Clinical data from our study suggested that in BAG3 mutation carriers acute onset DCM with hemodynamic compromise may be triggered by infection. CONCLUSIONS: BAG3 point mutations and large deletions are relatively frequent cause of DCM. Delayed DCM onset associated with truncating vs. non-truncating mutations may be important for genetic counseling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Cardiomiopatia Dilatada/genética , Genótipo , Mutação , Fenótipo , Sequência de Bases , Cardiomiopatia Dilatada/patologia , Primers do DNA , Éxons , Feminino , Humanos , Masculino , Linhagem , Polônia , Reação em Cadeia da Polimerase em Tempo Real
17.
Klin Oczna ; 116(2): 127-9, 2014.
Artigo em Polonês | MEDLINE | ID: mdl-25345292

RESUMO

Sebaceous carcinoma of the eyelid is a very rare, slow growing, malignant tumor. Most ocular sebaceous carcinomas originate in the tarsal meibomian glands. It commonly occurs in the sixth to eighth decade of life, with preponderance for women and Asians. The upper eyelid is affected more frequently. The disease can spread directly by orbital invasion, lymphatic spread to regional lymph nodes and hematogenous spread to distant organs. Correct diagnosis of sebaceous carcinoma is often delayed due to its resemblance to a variety of benign conditions of the eyelids such as chalasion or chronic blepharoconjunctivitis. This paper presents cases illustrating two clinical forms of sebaceous carcinoma (spreading and nodular), discusses clinical manifestation, differential diagnostic difficulties and therapy.


Assuntos
Adenocarcinoma Sebáceo/cirurgia , Neoplasias Palpebrais/cirurgia , Recidiva Local de Neoplasia , Neoplasias das Glândulas Sebáceas/cirurgia , Adenocarcinoma Sebáceo/patologia , Idoso , Neoplasias Palpebrais/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos , Prognóstico , Neoplasias das Glândulas Sebáceas/patologia , Resultado do Tratamento
18.
Postepy Dermatol Alergol ; 31(6): 405-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25610357

RESUMO

Lipodystrophies are a wide group of diseases with various etiology, mainly genetic, metabolic or autoimmune. The treatment of these diseases is chronic and not always effective. Major concerns for patients with lipodystrophies are also esthetic defects, especially deformities in the face, neck and upper limbs. There are many surgical methods that can be used to improve patient's appearance like fillers, autologous fat transfer and skin flaps. The aim of this paper is to present and discuss surgical techniques used for correction of lipoatrophy and other skin lesions present in lupus erythematosus. In the first presented patient, lipodermal grafts were performed in two stages (first - to both zygomatic areas, the second - to both nasolabial folds). Moreover, the patient was qualified for arm scar plasty. Deepithelialized skin in the affected area was covered with advanced local skin flaps. In the second patient, an extensive scarring lesion on the scalp was excised and the defect was closed with an expanded scalp flap. Patients with lipodystrophies may require aesthetic surgical procedures to improve their appearance. In patients with lupus erythematosus, autologous fat graft in the face area seems to be a safe and effective method of refilling the volume of atrophic tissues. On the basis of our experience, it is worth emphasizing that the process of fat graft resorption is typical. In patients with scalp scars, an effective method of their removal and hairline restoring is usage of the tissue expander.

20.
Pol Przegl Chir ; 96(3): 1-11, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979584

RESUMO

<b>Introduction:</b> Obesity, as one of the main health problems worldwide, is associated with an increased risk of developing mental and eating disorders and negative eating habits. Bariatric surgery allows for rapid weight loss and alleviates the symptoms of concomitant diseases in obese patients.<b>Aim:</b> Pre- and postoperative estimation of mental disorders and eating behaviors in patients after Roux-en-Y Gastric Bypass (RYGB).<b>Material and methods:</b> Analysis of data from up to 5 years of follow-up including clinical examination and questionnaires.<b>Results:</b> Following parameters decreased after RYGB: anxiety and hyperactivity from 32.81% to 21.88%, mood disorders - 31.25% to 20.31%, substance abuse - 40.63% to 28.13%, emotional eating - 76.56% to 29.69%, binge eating - 50% to 6.25%, night eating - 87.5% to 20.31%. Postoperative rates of: negative eating habits, daily intake of calories and sweetened beverages, flatulence, constipation, and abdominal pain decreased, while the rate of food intolerance and emesis increased.<b>Conclusions:</b> In our patients, the occurrence of: mental and eating disorders, negative eating habits, daily calories, sweetened beverages, coffee intake decreased after weight loss (as a result of RYGB), but water, vegetables and fruit consumption increased. Lower rate of flatulence, constipation, and abdominal pain, but higher of food intolerance and emesis were also confirmed after RYGB.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Derivação Gástrica , Humanos , Feminino , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Masculino , Adulto , Obesidade Mórbida/cirurgia , Obesidade Mórbida/psicologia , Pessoa de Meia-Idade , Saúde Mental , Transtornos Mentais/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/psicologia , Redução de Peso , Comportamento Alimentar/psicologia
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