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1.
Neurol Neurochir Pol ; 57(4): 387-391, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37341191

RESUMEN

INTRODUCTION: In this paper, we have analysed all hand glomangioma cases referred to our clinic in the context of symptoms, time to diagnosis, and the role of surgical resection of the lesion. MATERIAL AND METHODS: We have collected the following data: the presence of risk factors, manifestation, time to diagnosis, the treatment applied, and follow-up of patients. RESULTS: We have collected medical records from six patients, three males and three females. The median age was 45 (IQR: 29.5-65.75). The main symptom in all patients was severe pain and tenderness. The first-choice physician(s) were: general practitioners, general surgeons, and neurologists. The median time to diagnosis was 7 (IQR: 5-10) years. The main complaint of our patients was severe pain - 9 (IQR: 9-10) on the VAS scale, which was significantly alleviated after surgical treatment - 0 (IQR: 0-0; p = 0.043). CONCLUSIONS: Extremely long times to final diagnosis, and excellent outcomes of surgical treatment, highlight the necessity of raising awareness of glomangiomas among clinicians.


Asunto(s)
Tumor Glómico , Neoplasias Cutáneas , Masculino , Femenino , Humanos , Persona de Mediana Edad , Tumor Glómico/diagnóstico , Tumor Glómico/cirugía , Tumor Glómico/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Mano/cirugía , Diagnóstico Diferencial
2.
J Clin Med ; 11(15)2022 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-35956164

RESUMEN

Intramedullary spinal cord abscesses (ISCA) are rare. Typical symptoms include signs of infection and neurological deficits. Symptoms among (younger) children can be highly uncharacteristic. Therefore, prompt and proper diagnoses may be difficult. Typical therapeutic options include antibiotics and neurosurgical exploration and drainage. In this review, we analyze published cases of ISCA among children. Most pediatric cases were found to be under the age of 6 years. The typical symptoms included motor deficits in 89.06%, infection signs in 85.94%, and sensory deficits in 39.06%. Urinary dysfunction was observed in 43.75%, and bowel dysfunction in 17.19%. The predisposing factors included dermal sinuses, (epi)dermoid cysts, prior infection, iatrogenic disorder, and trauma. The most common pathogens were: Staphylococcus aureus, Mycobacterium tuberculosis, Escherichia coli, and Proteus mirabilis. The pediatric population has good outcomes as 45.93% of patients had complete neurological recovery and only 26.56% had residual neurological deficits. Fifteen (23.44%) had persistent neurological deficits. Only one (1.56%) patient died with an ISCA. In two (3.13%) cases, there were no details about follow-up examinations.

3.
Front Mol Neurosci ; 15: 923089, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860499

RESUMEN

Neurovascular compression syndromes (NVC) are challenging disorders resulting from the compression of cranial nerves at the root entry/exit zone. Clinically, we can distinguish the following NVC conditions: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Also, rare cases of geniculate neuralgia and superior laryngeal neuralgia are reported. Other syndromes, e.g., disabling positional vertigo, arterial hypertension in the course of NVC at the CN IX-X REZ and torticollis, have insufficient clinical evidence for microvascular decompression. The exact pathomechanism leading to characteristic NVC-related symptoms remains unclear. Proposed etiologies have limited explanatory scope. Therefore, we have examined the underlying pathomechanisms stated in the medical literature. To achieve our goal, we systematically reviewed original English language papers available in Pubmed and Web of Science databases before 2 October 2021. We obtained 1694 papers after eliminating duplicates. Only 357 original papers potentially pertaining to the pathogenesis of NVC were enrolled in full-text assessment for eligibility. Of these, 63 were included in the final analysis. The systematic review suggests that the anatomical and/or hemodynamical changes described are insufficient to account for NVC-related symptoms by themselves. They must coexist with additional changes such as factors associated with the affected nerve (e.g., demyelination, REZ modeling, vasculature pathology), nucleus hyperexcitability, white and/or gray matter changes in the brain, or disturbances in ion channels. Moreover, the effects of inflammatory background, altered proteome, and biochemical parameters on symptomatic NVC cannot be ignored. Further studies are needed to gain better insight into NVC pathophysiology.

4.
Histochem Cell Biol ; 157(5): 525-546, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35230485

RESUMEN

Interleukin (IL)-6, a known proinflammatory cytokine, is released in both visceral adipose tissue and contracting skeletal muscle. In this study, we used microRNA profiling as a screening method to identify miRNA species modified by IL-6 treatment in mouse 3T3-L1 adipocytes. miRNA microarray analysis and qRT-PCR revealed increased expression of miR-146b-3p in adipocytes exposed to IL-6 (1 ng/ml) during 8-day differentiation. On the basis of ontological analysis of potential targets, selected proteins associated with cytoskeleton and transport were examined in the context of adipocyte response to insulin, using immunofluorescence and confocal microscopy. We concluded that IL-6: (i) does not affect insulin action on actin cellular distribution; (ii) modulates the effect of insulin on myosin light chain kinase (Mylk) distribution by preventing its shift toward cytoplasm; (iii) mimics the effect of insulin on dynein distribution by increasing its near-nuclear accumulation; (iv) mimics the effect of insulin on glucose transporter Glut4 distribution, especially by increasing its near-nuclear accumulation; (v) supports insulin action on early endosome marker Rab4A near-nuclear accumulation. Moreover, as IL-6 did not disturb insulin-dependent glucose uptake, our results do not confirm the IL-6-induced impairment of insulin action observed in some in vitro studies, suggesting that the effect of IL-6 is dose dependent.


Asunto(s)
Interleucina-6 , MicroARNs , Células 3T3-L1 , Adipocitos/metabolismo , Animales , Proteínas del Citoesqueleto/metabolismo , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Insulina/metabolismo , Insulina/farmacología , Interleucina-6/metabolismo , Ratones , MicroARNs/metabolismo
5.
J Clin Med ; 10(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805774

RESUMEN

We developed a practical and cost-effective method of production of a 3D-printed model of the arterial Circle of Willis of patients treated because of an intracranial aneurysm. We present and explain the steps necessary to produce a 3D model from medical image data, and express the significant value such models have in patient-specific pre-operative planning as well as education. A Digital Imaging and Communications in Medicine (DICOM) viewer is used to create 3D visualization from a patient's Computed Tomography Angiography (CTA) images. After generating the reconstruction, we manually remove the anatomical components that we wish to exclude from the print by utilizing tools provided with the imaging software. We then export this 3D reconstructions file into a Standard Triangulation Language (STL) file which is then run through a "Slicer" software to generate a G-code file for the printer. After the print is complete, the supports created during the printing process are removed manually. The 3D-printed models we created were of good accuracy and scale. The median production time used for the models described in this manuscript was 4.4 h (range: 3.9-4.5 h). Models were evaluated by neurosurgical teams at local hospital for quality and practicality for use in urgent and non-urgent care. We hope we have provided readers adequate insight into the equipment and software they would require to quickly produce their own accurate and cost-effective 3D models from CT angiography images. It has become quite clear to us that the cost-benefit ratio in the production of such a simplified model is worthwhile.

6.
Vaccines (Basel) ; 9(3)2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33806641

RESUMEN

Healthcare workers are particularly exposed to biological risk during their daily occupational activities. Nowadays, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become one of the most widespread infectious agents. In the current study, we performed a survey on the attitude and behavior of Polish healthcare workers (HCW), which comprise physicians (MD) and administrative healthcare assistants (HA) towards the Coronavirus Disease 2019 (COVID-19) vaccination. Our study involved 2300 subjects (42.17% female; 10.96% MD; 5.87% HA). The evaluation was conducted using a Google Forms survey based on original questions and the Depression, Anxiety and Stress Scale-21 Items questionnaire. HCW significantly more often demonstrated their willingness to get vaccinated against the SARS-CoV-2 as compared to the control group (82.95% vs. 54.31%, respectively). The main concern, as regards all groups, was the development of long-term side effects after getting COVID-19 vaccine. The study revealed that depression significantly affects the willingness to get vaccinated. The readiness was significantly strengthened by positive medical history of recommended vaccinations, fear of catching COVID-19, as well as fear of passing on the disease to the relatives. Overall, the percentage of HCW, who want to be vaccinated against COVID-19 remains unsatisfactory. Further works exploring this subject are needed to take a step closer to achieving the herd immunity in the era of the COVID-19 pandemic.

7.
Front Immunol ; 12: 604066, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33679741

RESUMEN

Expansion protocols for human T lymphocytes using magnetic beads, which serve as artificial antigen presenting cells (aAPCs), is well-studied. Yet, the efficacy of magnetic beads for propagation and functionality of peripheral blood lymphocytes (PBLs) isolated from companion dogs still remains limited. Domestic dog models are important in immuno-oncology field. Thus, we built the platform for induction of canine PBLs function, proliferation and biological activity using nano-sized magnetic beads (termed as MicroBeads) coated with anti-canine CD3 and CD28 antibodies. Herein we reveal that activation of canine PBLs via MicroBeads induces a range of genes involved in immediate-early response to T cell activation in dogs. Furthermore, canine T lymphocytes are effectively activated by MicroBeads, as measured by cluster formation and induction of activation marker CD25 on canine T cells as quickly as 24 h post stimulation. Similar to human T cells, canine PBLs require lower activation signal strength for efficient proliferation and expansion, as revealed by titration studies using a range of MicroBeads in the culture. Additionally, the impact of temperature was assessed in multiple stimulation settings, showing that both 37°C and 38.5°C are optimal for the expansion of canine T cells. In contrast to stimulation using plant mitogen Concanavalin A (ConA), MicroBead-based activation did not increase activation-induced cell death. In turn, MicroBeads supported the propagation of T cells with an effector memory phenotype that secreted substantial IL-2 and IFN-γ. Thus, MicroBeads represent an accessible and affordable tool for conducting immunological studies on domestic dog models. Similarities in inducing intracellular signaling pathways further underscore the importance of this model in comparative medicine. Presented herein MicroBead-based expansion platforms for canine PBLs may benefit adoptive immunotherapy in dogs and facilitate the design of next-generation clinical trials in humans.


Asunto(s)
Proliferación Celular , Activación de Linfocitos , Linfocitos T/inmunología , Animales , Células Presentadoras de Antígenos/citología , Células Presentadoras de Antígenos/inmunología , Perros , Linfocitos T/citología
8.
Cancers (Basel) ; 13(5)2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33668874

RESUMEN

To monitor redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving methods are required. We used Raman spectroscopy and Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues at 532 nm, 633 nm, 785 nm. We identified the oncogenic processes that characterize human infiltrating ductal carcinoma (IDC) and human brain tumors: gliomas; astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. We visualized localization of cytochromes by Raman imaging in the breast and brain tissues and analyzed cytochrome c vibrations at 750, 1126, 1337 and 1584 cm-1 as a function of malignancy grade. We found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers and correlates with the grade of cancer. We showed that Raman imaging provides additional insight into the biology of astrocytomas and breast ductal invasive cancer, which can be used for noninvasive grading, differential diagnosis.

9.
Vaccines (Basel) ; 9(2)2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33562872

RESUMEN

Since physicians play a key role in vaccination, the initial training of medical students (MS) should aim to help shape their attitude in this regard. The beginning of vaccination programs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an excellent time to assess the attitudes held by both medical and non-medical students regarding vaccination. A 51- to 53-item questionnaire including the Depression, Anxiety and Stress Scale was administered to 1971 students (49.21% male; 34.86% MS); two career-related questions were also addressed to the MS. The majority of surveyed students indicated a desire to get vaccinated against SARS-CoV-2, with more medical than non-medical students planning to get vaccinated (91.99% vs. 59.42%). The most common concern about SARS-CoV-2 infection was the risk of passing on the disease to elderly relatives. While conspiracy theories regarding the COVID-19 vaccine are less popular among MS, both groups indicated concerns that vaccines may cause autism is equally common (~5%). Further studies exploring social attitudes towards the SARS-CoV-2 vaccine are a necessary first step to optimizing vaccination programs and achieving herd immunity.

10.
Cell Tissue Res ; 380(1): 155-172, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31820147

RESUMEN

Interleukin (IL)-6 is a proinflammatory cytokine released in injured and contracting skeletal muscles. In this study, we examined cellular expression of proteins associated with cytoskeleton organization and cell migration, chosen on the basis of microRNA profiling, in rat primary skeletal muscle cells (RSkMC) treated with IL-6 (1 ng/ml) for 11 days. MiRNA microarray analysis and qRT-PCR revealed increased expression of miR-154-3p and miR-338-3p in muscle cells treated with IL-6. Pacsin3 was downregulated post-transcriptionally by IL-6, but not by IGF-I. Ephrin4A protein was increased both in IL-6- and IGF-I-treated myocytes. IL-6, but not IGF-I, stimulated migratory ability of RSkMC, examined in wound healing assay. Alpha-actinin protein was slightly augmented in RSKMC treated with IL-6, similarly to IGF-I. IL-6, but not IGF-I, upregulated desmin in differentiating RSkMC. IL-6 supplementation caused accumulation of alpha-actinin and desmin in near-nuclear area of muscle cells, which was manifested by increased ratio: mean near-nuclear fluorescence/mean peripheral cytoplasm fluorescence of these proteins. We concluded that IL-6, a known proinflammatory cytokine and a physical activity-associated myokine, acting during differentiation of primary skeletal muscle cells, alters expression of nonmuscle-specific miRNAs. This cytokine causes differential effects on pacsin-3 and ephrinA4, through post-transcriptional inhibition and stimulation, respectively. IL-6-exerted modifications of cytoskeletal proteins in muscle cells include both transcriptional (desmin and dynein heavy chain 5) and post-transcriptional activation (alpha-actinin). Moreover, IL-6 augments near-nuclear distribution of cytoskeletal proteins, alpha-actinin and desmin and promotes migration of myocytes. Such effects suggest that IL-6 plays a role during skeletal muscle regeneration, acting through mechanisms independent of regulation of myogenic program.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Efrina-A4/biosíntesis , Interleucina-6/farmacología , Mioblastos Esqueléticos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Diferenciación Celular/efectos de los fármacos , Proteínas del Citoesqueleto/biosíntesis , Proteínas del Citoesqueleto/genética , Modelos Animales de Enfermedad , Efrina-A4/genética , Factor I del Crecimiento Similar a la Insulina/farmacología , MicroARNs/biosíntesis , MicroARNs/genética , MicroARNs/metabolismo , Mioblastos Esqueléticos/citología , Mioblastos Esqueléticos/efectos de los fármacos , Procesamiento Postranscripcional del ARN , Ratas , Proteínas Recombinantes/farmacología , Transcripción Genética
11.
J Cell Physiol ; 234(11): 19675-19690, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-30945300

RESUMEN

Interleukin (IL)-8 is released both in visceral adipose tissue and in contracting skeletal muscles. In this study, we examined cellular pathways associated with muscle hypertrophy, chosen on the basis of microRNA profiling, in differentiating rat primary skeletal muscle cells (RSkMC) treated with IL-8 (1 ng/ml) for 11 days. IL-8 increased myocilin expression, Akt phosphorylation, FoxO3 dispersion throughout the cytoplasm, and reduced FoxO3 level. IL-8 decreased the expression of atrogin and MuRF1 and increased myotube length and diameter. We concluded that IL-8 present in extracellular environment of myoblasts induced to differentiation stimulates expression of myocilin, a protein important for skeletal muscle hypertrophy. This phenomenon was associated with: (a) activation of myogenic transcription, (b) increased phosphorylation and activation of PKB/Akt, leading to (c) cytoplasm distribution and degradation of a transcription factor FoxO3, (d) decreased expression of gene markers of proteolysis, atrogin and Murf1, and (e) increased myotube length and diameter. In this regard, IL-8 affects skeletal muscle cells similarly to IGF-I and can be considered as a potent anticatabolic factor for skeletal muscle.


Asunto(s)
Proteínas del Citoesqueleto/genética , Proteínas del Ojo/genética , Proteína Forkhead Box O3/genética , Glicoproteínas/genética , Interleucina-8/genética , Desarrollo de Músculos/genética , Músculo Esquelético/metabolismo , Animales , Diferenciación Celular/genética , Factor I del Crecimiento Similar a la Insulina/genética , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Mioblastos/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Transducción de Señal , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genética
12.
Brief Bioinform ; 20(6): 2299-2305, 2019 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-30247502

RESUMEN

CABS-dock is a computational method for protein-peptide molecular docking that does not require predefinition of the binding site. The peptide is treated as fully flexible, while the protein backbone undergoes small fluctuations and, optionally, large-scale rearrangements. Here, we present a specific CABS-dock protocol that enhances the docking procedure using fragmentary information about protein-peptide contacts. The contact information is used to narrow down the search for the binding peptide pose to the proximity of the binding site. We used information on a single-chosen and randomly chosen native protein-peptide contact to validate the protocol on the peptiDB benchmark. The contact information significantly improved CABS-dock performance. The protocol has been made available as a new feature of the CABS-dock web server (at http://biocomp.chem.uw.edu.pl/CABSdock/). SHORT ABSTRACT: CABS-dock is a tool for flexible docking of peptides to proteins. In this article, we present a protocol for CABS-dock docking driven by information about protein-peptide contact(s). Using information on individual protein-peptide contacts allows to improve the accuracy of CABS-dock docking.


Asunto(s)
Simulación del Acoplamiento Molecular , Péptidos/metabolismo , Proteínas/metabolismo , Unión Proteica
13.
Biomed Eng Online ; 16(Suppl 1): 71, 2017 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-28830442

RESUMEN

BACKGROUND: Many protein-protein interactions are mediated by a short linear motif. Usually, amino acid sequences of those motifs are known or can be predicted. It is much harder to experimentally characterize or predict their structure in the bound form. In this work, we test a possibility of using flexible docking of a short linear motif to predict the interaction interface of the EphB4-EphrinB2 complex (a system extensively studied for its significance in tumor progression). METHODS: In the modeling, we only use knowledge about the motif sequence and experimental structures of EphB4-EphrinB2 complex partners. The proposed protocol enables efficient modeling of significant conformational changes in the short linear motif fragment during molecular docking simulation. For the docking simulations, we use the CABS-dock method for docking fully flexible peptides to flexible protein receptors (available as a server at http://biocomp.chem.uw.edu.pl/CABSdock/ ). Based on the docking result, the protein-protein complex is reconstructed and refined. RESULTS: Using this novel protocol, we obtained an accurate EphB4-EphrinB2 interaction model. CONCLUSIONS: The results show that the CABS-dock method may be useful as the primary docking tool in specific protein-protein docking cases similar to EphB4-EphrinB2 complex-that is, where a short linear motif fragment can be identified.


Asunto(s)
Efrina-B2/química , Efrina-B2/metabolismo , Simulación del Acoplamiento Molecular , Receptor EphB4/química , Receptor EphB4/metabolismo , Secuencias de Aminoácidos , Unión Proteica
14.
Biomed Eng Online ; 16(Suppl 1): 73, 2017 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-28830545

RESUMEN

BACKGROUND: The characterization of protein-peptide interactions is a challenge for computational molecular docking. Protein-peptide docking tools face at least two major difficulties: (1) efficient sampling of large-scale conformational changes induced by binding and (2) selection of the best models from a large set of predicted structures. In this paper, we merge an efficient sampling technique with external information about side-chain contacts to sample and select the best possible models. METHODS: In this paper we test a new protocol that uses information about side-chain contacts in CABS-dock protein-peptide docking. As shown in our recent studies, CABS-dock enables efficient modeling of large-scale conformational changes without knowledge about the binding site. However, the resulting set of binding sites and poses is in many cases highly diverse and difficult to score. RESULTS: As we demonstrate here, information about a single side-chain contact can significantly improve the prediction accuracy. Importantly, the imposed constraints for side-chain contacts are quite soft. Therefore, the developed protocol does not require precise contact information and ensures large-scale peptide flexibility in the broad contact area. CONCLUSIONS: The demonstrated protocol provides the extension of the CABS-dock method that can be practically used in the structure prediction of protein-peptide complexes guided by the knowledge of the binding interface.


Asunto(s)
Simulación del Acoplamiento Molecular , Péptidos/química , Péptidos/metabolismo , Proteínas/química , Proteínas/metabolismo , Sitios de Unión , Unión Proteica , Conformación Proteica
15.
Cell Biol Int ; 41(4): 457-463, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28191740

RESUMEN

The purpose of the study was to examine the effect of interleukins, IL-6, IL-8, and IL-15, on insulin-mediated redistribution of Rab4a, an early endosome marker, in mouse 3T3-L1 adipocytes. The interleukins did not affect cell viability; however, cell number was slightly but significantly higher in cultures exposed to IL-8 and IL-15. IL-8 and IL-15 decreased lipid storage in adipocytes, whereas IL-6 had no effect. Rab4A showed cytoplasmic localization, and in control unstimulated adipocytes it was found primarily nearby nucleus, that was supported by cellular fluorescence distribution profile, and by calculated indices, that is, high percentage of near-nuclear area fluorescence and a low mean peripheral cytoplasmic fluorescence/mean near-nuclear fluorescence ratio. Insulin stimulation (100 nmol/l, 30 min) altered the cytoplasmic localization of Rab4a in control adipocytes, which was manifested by its redistribution towards plasma membrane. This effect of insulin was prevented in adipocytes exposed to IL-6, IL-8, or IL-15. We concluded that insulin-dependent Rab4a redistribution, probably reflecting stimulation of vesicle-mediated transport, is inhibited in adipocytes subjected to differentiation in the presence of IL-6, IL-8, or IL-15. Such alterations may be involved in the mechanisms contributing to development of insulin resistance associated with inflammation; however, further studies in this field are required.


Asunto(s)
Adipocitos/enzimología , Insulina/fisiología , Interleucina-6/fisiología , Interleucina-8/fisiología , Proteínas de Unión al GTP rab4/metabolismo , Células 3T3-L1 , Animales , Citoplasma/enzimología , Interleucina-15/fisiología , Ratones , Transporte de Proteínas
16.
Neurol Neurochir Pol ; 50(3): 219-25, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27154453

RESUMEN

INTRODUCTION: Neurofibromatosis type 2 (NF2) and schwannomatosis are entities that may, due to the similarity of clinical symptoms, cause diagnostic difficulties. Incidence rate of both diseases is similar and estimated between 1:25,000 and 1:40,000. The genes associated with the development of the aforementioned disorders are located on chromosome 22 and lay in proxmity. Schwannomatosis is characterized by an incomplete penetrance and the risk of its transmission to the offspring is significantly lower than in the case of NF 2. Schwannomatosis clinical characteristic is similar to the NF2, however vestibular schwannomas are not present. Therefore the imaging studies evaluated by an experienced radiologist play a key role in the diagnostic process. CASE REPORT: Forty two-year-old female hospitalized three times because of the tumors of the spinal canal was admitted to the Department of Neurosurgery and Peripheral Nerve Surgery in 2008 because of the cervical pain syndrome with concomitant headache. She was diagnosed with a schwannomatosis, recently distinguished, the third form of neurofibromatosis. MRI imaging revealed craniocervical junction tumor. Suboccipital craniectomy with concomitant C1-C2 laminectomy was done in order to remove the lesion. After the surgery the patient did not present any deficits in neurological examination and was discharged from hospital in good general condition. CONCLUSIONS: The patient was diagnosed with schwannomatosis, recently established neurofibromatosis entity which may resemble NF2 clinically. In patients after the age of 30, in whom we observe multiple schwannomas without the concomitant hearing impairment, the diagnosis of schwannomatosis is very likely.


Asunto(s)
Neurilemoma/diagnóstico , Neurofibromatosis/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Neurilemoma/cirugía , Neurofibromatosis/cirugía , Neurofibromatosis 2/diagnóstico , Neoplasias Cutáneas/cirugía
17.
Methods ; 93: 72-83, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26165956

RESUMEN

Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental and theoretical research. Computational modeling of the structure of protein-peptide interactions is usually divided into two stages: prediction of the binding site at a protein receptor surface, and then docking (and modeling) the peptide structure into the known binding site. This paper presents a comprehensive CABS-dock method for the simultaneous search of binding sites and flexible protein-peptide docking, available as a user's friendly web server. We present example CABS-dock results obtained in the default CABS-dock mode and using its advanced options that enable the user to increase the range of flexibility for chosen receptor fragments or to exclude user-selected binding modes from docking search. Furthermore, we demonstrate a strategy to improve CABS-dock performance by assessing the quality of models with classical molecular dynamics. Finally, we discuss the promising extensions and applications of the CABS-dock method and provide a tutorial appendix for the convenient analysis and visualization of CABS-dock results. The CABS-dock web server is freely available at http://biocomp.chem.uw.edu.pl/CABSdock/.


Asunto(s)
Modelos Moleculares , Simulación del Acoplamiento Molecular/métodos , Péptidos/metabolismo , Proteínas/metabolismo , Navegador Web , Sitios de Unión/fisiología , Péptidos/química , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Proteínas/química
18.
Nucleic Acids Res ; 43(W1): W419-24, 2015 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-25943545

RESUMEN

Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock.


Asunto(s)
Simulación del Acoplamiento Molecular/métodos , Péptidos/química , Conformación Proteica , Programas Informáticos , Sitios de Unión , Internet , Péptidos/metabolismo , Proteínas/química , Proteínas/metabolismo
19.
Cell Biol Int ; 39(9): 1044-52, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25857830

RESUMEN

The purpose of the study was to examine mechanisms controlling cell cycle progression/arrest and differentiation of mouse C2C12 myoblasts exposed to long-chain saturated fatty acid salt, palmitate. Treatment of proliferating myoblasts with palmitate (0.1 mmol/l) markedly decreased myoblast number. Cyclin A and cyclin D1 levels decreased, whereas total p21 and p21 complexed with cyclin-dependent kinase-4 (cdk4) increased in myoblasts treated with palmitate. In cells induced to differentiation addition of palmitate augmented the level of cyclin D3, the early (myogenin) and late (α-actinin, myosin heavy chain) markers of myogenesis, and caused an increase of myotube diameter. In conclusion, exposure to palmitate inhibits proliferation of myoblasts through a decrease in cyclin A and cyclin D1 levels and an increase of p21-cdk4 complex formation; however, it promotes cell cycle exit, myogenic differentiation and myotube growth.


Asunto(s)
Mioblastos Esqueléticos/efectos de los fármacos , Palmitatos/farmacología , Animales , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Ciclina A/efectos de los fármacos , Ciclina D1/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ratones , Fibras Musculares Esqueléticas/efectos de los fármacos , Mioblastos Esqueléticos/citología , Mioblastos Esqueléticos/metabolismo , Miogenina/efectos de los fármacos
20.
J Interferon Cytokine Res ; 35(2): 89-99, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25237846

RESUMEN

The purpose of the present study was to investigate the effect of interferon (IFN)-γ on the transcriptomic profile of differentiating mouse C2C12 myogenic cells. Global gene expression was evaluated using whole mouse genome oligonucleotide microarrays, and the results were validated through real-time PCR. IFN-γ (1 ng/mL) increased myoblast proliferation but decreased cell respiration and myosin heavy chain content and slightly decreased the fusion index in differentiating C2C12 cell cultures. The genes upregulated through IFN-γ were involved in cell cycle; regulation of cell proliferation; programmed cell death; chemotaxis; and cytokine, growth factor, and peptidase activity, whereas the genes downregulated through IFN-γ primarily contributed to the regulation of transcription, cell-cell signaling, nitrogen compound biosynthesis, ser/thr protein kinase signaling, and regulation of the Wnt pathway. In conclusion, IFN-γ affects the expression of numerous genes associated with the regulation of several processes in myogenesis. The effects of IFN-γ on cellular transcription include (1) alteration of cytokine/growth factor expression, promoting cell proliferation and migration but inhibiting differentiation, (2) impairment of pro-myogenic transcription, (3) disruption of cell adhesion and sarcolemma/cytoskeleton organization, and (4) increased peptidase activity leading to enhanced proteolysis and apoptosis.


Asunto(s)
Regulación de la Expresión Génica/fisiología , Interferón gamma/metabolismo , Desarrollo de Músculos/fisiología , Proteínas Musculares/biosíntesis , Transcripción Genética/fisiología , Vía de Señalización Wnt/fisiología , Animales , Apoptosis/fisiología , Línea Celular , Proliferación Celular/fisiología , Ratones
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