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1.
Eur Urol Open Sci ; 62: 91-98, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38486615

RESUMO

Background: The optimal treatment for complex urethral stricture (CUS) is yet to be determined. Comparisons of methods based on validated questionnaires or objective outcome measures are lacking. Objective: To compare proximal urethrostomy and urethroplasty for CUS using objective measures and validated questionnaires, and to evaluate trends in subgroups of patients who underwent proximal urethrostomy as the intended definitive treatment versus first-stage urethroplasty. Design setting and participants: We identified all patients who underwent proximal urethrostomy at our center from 2004 to 2021. The control group comprised patients who underwent urethroplasty for CUS (strictures >6 cm, recurrent posturethroplasty strictures, or CUS due to lichen sclerosus or past hypospadias surgery). Outcome measurements and statistical analysis: The primary outcome was a recurrent stricture at a minimal follow-up of 1 yr. The secondary outcomes included validated questionnaires, uroflowmetry, and residual urine volume. Survival was compared by a Kaplan-Meier analysis. Results and limitations: The study included 57 proximal urethrostomy and 75 urethroplasty patients. Results for these two groups were as follows: the cumulative incidence of stricture recurrence over a median follow-up of 46 mo was 22.6% for proximal urethrostomy versus 36.2% for urethroplasty (p = 0.106); no statistically significant differences were observed between groups in terms of postoperative quality of urination or life, satisfaction with outcome, and erectile function. Both groups had a significant improvement in urinary flow after surgery (19.65 vs 20.29 ml/s), with no difference between the groups (p = 0.796); the proximal urethrostomy group had a significant improvement in postvoid residual after surgery, but there was no difference between the groups in the last follow-up visit (79.16 vs 52.03 ml; p = 0.245). A subgroup analysis of the proximal urethrostomy group showed no significant differences in cumulative primary or secondary outcomes. Limitations included the retrospective design and the relatively small study population. Conclusions: Comparisons of the two groups revealed no significant differences in stricture recurrence, results of validated questionnaires, or objective measures of urination. Patient summary: Proximal urethrostomy is equivalent to urethral reconstruction, and it should be offered as a viable solution for complex urethral stricture.

2.
Plast Reconstr Surg Glob Open ; 8(12): e3286, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33425598

RESUMO

Radiofrequency energy thermally induces collagen contraction and remodeling. The resultant dermal tightening is well established. However, facial aging encompasses also deeper layers of collagen-containing tissues. We present a deep layer radiofrequency-based thermo-coagulative technique for cervicofacial contouring and evaluate its efficacy. METHODS: This prospective single center study was conducted from June 2017 to June 2018 and included 10 women. Echogenicity and thickness of layers 1-5 of the lower face, lateral neck, and submental regions were sonographically measured at baseline and at 6 weeks postoperatively. Echogenicity analysis was based on the number of high echogenic pixels counted and processed using Matlab-based image application (The Mathworks, Natick, Mass.). Clinical outcome at 12 months postoperatively was evaluated by 2 independent evaluators using a validated 5-point lower face improvement scale and the Merz jawline scale (0-4). Patient satisfaction and adverse effects were recorded. RESULTS: Mean age was 60.2 years (range, 52-76). A statistically significant increase in echogenicity (P ≤ 0.02) and a decrease in thickness (P = 0.01) was noted. Echogenicity increased at 149%, 78%, and 60%, for the lateral neck, lower face, and submental region, respectively. The corresponding decrease in thickness per site was 16%, 6%, and 19%. The average physicians' improvement in lower face contour was 3.8, and the Merz jawline scale was improved from 2.85 at baseline to 1.05 at 12 months postoperatively. Patient satisfaction was high. Side effects were minimal. CONCLUSIONS: Deep layer radiofrequency-based technology thermally induces profound soft tissue tightening and neocollagenesis. It is a safe and effective technique for cervicofacial contouring in selected patients.

3.
Nucleic Acids Res ; 47(12): 6330-6338, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31045216

RESUMO

In-frame stop codons mark the termination of translation. However, post-termination ribosomes can reinitiate translation at downstream AUG codons. In mammals, reinitiation is most efficient when the termination codon is positioned close to the 5'-proximal initiation site and around 78 bases upstream of the reinitiation site. The phenomenon was studied mainly in the context of open reading frames (ORFs) found within the 5'-untranslated region, or polycicstronic viral mRNA. We hypothesized that reinitiation of translation following nonsense mutations within the main ORF of p53 can promote the expression of N-truncated p53 isoforms such as Δ40, Δ133 and Δ160p53. Here, we report that expression of all known N-truncated p53 isoforms by reinitiation is mechanistically feasible, including expression of the previously unidentified variant Δ66p53. Moreover, we found that significant reinitiation of translation can be promoted by nonsense mutations located even 126 codons downstream of the 5'-proximal initiation site, and observed when the reinitiation site is positioned between 6 and 243 bases downstream of the nonsense mutation. We also demonstrate that reinitiation can stabilise p53 mRNA transcripts with a premature termination codon, by allowing such transcripts to evade the nonsense mediated decay pathway. Our data suggest that the expression of N-truncated proteins from alleles carrying a premature termination codon is more prevalent than previously thought.


Assuntos
Códon sem Sentido , Iniciação Traducional da Cadeia Peptídica , Proteína Supressora de Tumor p53/genética , Linhagem Celular , Células HEK293 , Humanos , Degradação do RNAm Mediada por Códon sem Sentido , Regiões Promotoras Genéticas , Estabilidade de RNA , RNA Mensageiro/metabolismo , Deleção de Sequência , Proteína Supressora de Tumor p53/biossíntese
4.
Dermatol Surg ; 45(5): 725-729, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30882504

RESUMO

BACKGROUND: Pigmentation is one of the few major characteristics according to which scars are evaluated. Data on the treatment of the hyperpigmented component of scars are sparse. OBJECTIVE: The authors aimed at evaluating the efficacy of the fractional 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) picosecond laser in the treatment of the hyperpigmented component of scars. METHODS: Sixteen patients with hyperpigmented scars underwent 3 to 8 treatment sessions at 3- to 6-week intervals with the 1,064-nm Nd:YAG picosecond laser (PicoWay, Candela, Resolve handpiece). The treatment response was evaluated by 2 noninvolved dermatologists on a global assessment scale (GAS) of 1 to 4. A Mexameter quantitatively evaluated the melanin content of the scar before and after laser treatments. RESULTS: The average GAS score of the 2 noninvolved dermatologists was 3.31 ± 0.57. The patients assessed their level of tolerance as good or excellent and their satisfaction level as moderate or high. The Mexameter showed that the melanin index decreased considerably (by 39.11 ± 11.58%) in all patients after treatment. CONCLUSION: The fractionated nonablative picosecond Nd:YAG laser was effective for the treatment of the hyperpigmented component of scars.


Assuntos
Cicatriz/radioterapia , Lasers de Estado Sólido/uso terapêutico , Transtornos da Pigmentação/radioterapia , Adolescente , Adulto , Idoso , Alumínio , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neodímio , Resultado do Tratamento , Ítrio
5.
Dermatol Surg ; 45(5): 711-717, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30908361

RESUMO

BACKGROUND: Microneedling fractional radiofrequency (FRF) and chemical peels are widely used for skin rejuvenation. OBJECTIVE: The authors aimed at evaluating the efficacy and safety of FRF and trichloroacetic acid 20% (TCA20%) peel in different combinations for determining the optimal treatment protocol. METHODS: In this prospective clinical comparison of 4 protocols (FRF alone, TCA20% alone, TCA20% before FRF [TCA→FRF], and TCA20% following FRF [FRF→TCA]), the patients underwent 3.8 ± 1.2 successive treatments of one protocol at 4- to 6-week intervals. The patients and 2 dermatologists evaluated improvement of pigmentation and dyschromia, erythema and blood vessels, laxity and wrinkling, and skin imperfections using a global aesthetic improvement scale (GAIS) and a 1 to 5 scoring system. The patients rated their satisfaction and reported adverse effects and reduced activity. Skin impedance and histological changes following the different protocols were also evaluated on 3 additional volunteers. RESULTS: Sixty-seven patients (age range 22-80 years) were studied. TCA→FRF caused skin impedance to decrease, yielding a more superficial and less-efficient penetration of FRF energy. FRF→TCA produced more significant improvement in overall facial skin appearance (GAIS) and most evaluated skin parameters. Adverse effects and satisfaction rates were similar for all approaches. CONCLUSION: FRF→TCA had the best synergistic effect on skin rejuvenation compared with FRF or TCA20% alone and TCA→FRF.


Assuntos
Abrasão Química/métodos , Técnicas Cosméticas , Terapia por Radiofrequência , Rejuvenescimento , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Ácido Tricloroacético/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Aesthet Surg J ; 38(3): 312-320, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29040367

RESUMO

BACKGROUND: The principle of dynamic muscular activity affecting eyebrow height and shape is well known. We postulate that similarly, dynamics of the fronto-galea-occipital muscles affect forehead height. OBJECTIVES: To present a forehead lift technique using Botulinum toxin injection and evaluate its clinical efficacy and safety. METHODS: Twenty-nine female patients comprised the study group. Forty units of prepared abobutolinumtoxinA (Dysport, 10 U/0.05 mL) were injected into 4 points in the hair-bearing scalp, simulating the points of frontalis origin. The glabella and forehead regions were treated with 50 U each. Standard photographs and measurements were taken before and at 2 weeks following treatment. Forehead height was measured bilaterally drawing a vertical line from mid-pupil to frontal hairline (MPFH) and from medial canthus to frontal hairline (MCFH). We assessed outcome differences in patients with low vs high forehead (cutoff value 5.5 cm forehead height). RESULTS: Mean age was 48 years (range, 29-66 years). Two weeks following treatment, mean frontal height had increased significantly in all measurement points (MCFH right: 4.1 ± 1.8 mm, MCFH left 4.4 ± 1.8 mm, MPFH right 4.4 ± 2.0 mm, MPFH left 4.7 ± 2.3 mm; P <0.001). Low forehead subgroup achieved significantly higher forehead lift compared with high forehead subgroup both in MCFH (6.9% ± 2.0% vs 5.3% ± 2.2%, P = 0.043) and MPFH (8.6% ± 2.5% vs 5.7% ± 2.6%, P = 0.008). No adverse events were documented in any participant. CONCLUSIONS: Botulinum toxin type A injection into frontalis origin can effectively and safely extend forehead height in selected patients. The effect of this technique is greater on patients with low foreheads.


Assuntos
Inibidores da Liberação da Acetilcolina/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Técnicas Cosméticas , Testa/anatomia & histologia , Envelhecimento da Pele/efeitos dos fármacos , Inibidores da Liberação da Acetilcolina/efeitos adversos , Adulto , Idoso , Toxinas Botulínicas Tipo A/efeitos adversos , Feminino , Testa/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Fotografação , Resultado do Tratamento
7.
ACS Appl Mater Interfaces ; 9(1): 868-875, 2017 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-28005334

RESUMO

UV-absorbing nanoparticles (NPs) and microparticles (MPs) were prepared by emulsion and dispersion copolymerization of the vinylic monomer 2-(2'-hydroxy-5'-methacryloxyethylphenyl)-2H-benzotriazole (Norbloc (NB)) with the crosslinking monomer divinylbenzene. The effect of the initiator concentration on the size and size distribution of the polyNB (PNB) particles was elucidated. Thin coatings of the formed PNB NPs or MPs of 19 ± 2 and 200 ± 25 nm dry diameter, respectively, onto polypropylene (PP) films were then prepared and characterized. Increasing the concentration or thickness of the PNB NP or MP thin coatings on the PP films decreased their UV transmittance, up to complete UV blocking with just 2 µm of a 4% NP coating. Migration of the UV-absorbing agents from the coated PP films was not observed during three years of storage at room temperature, offering a unique solution to current problems of migration of UV-absorbing additives. The thin coatings obtained by the PNB NPs were superior to those of the PNB MPs, in that no UV transmittance or loss of optical properties of the PP films were observed for the NP coatings, while the coatings produced by the PNB MPs resulted in damaged optical properties, particularly increasing the haze, and achieved incomplete UV blocking.

8.
J Mol Biol ; 428(15): 3013-25, 2016 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-27338200

RESUMO

Normal cellular homeostasis depends on tight regulation of gene expression, which requires the modulation of transcription factors' DNA-binding specificity. That said, the mechanisms that allow transcription factors to distinguish between closely related response elements following different cellular signals are not fully understood. In the tumor suppressor protein p53, acetylation of loop L1 residue Lys120 within the DNA-binding domain has been shown to promote the transcription of proapoptotic genes such as bax. Here, we report the crystal structures of Lys120-acetylated p53 DNA-binding domain in complex with a consensus response element and with the natural BAX response element. Our structural analyses reveal that Lys120 acetylation expands the conformational space of loop L1 in the DNA-bound state. Loop L1 flexibility is known to increase p53's DNA-binding specificity, and Lys120-acetylation-dependent conformational changes in loop L1 enable the formation of sequence-dependent DNA-binding modes for p53. Furthermore, binding to the natural BAX response element is accompanied by global conformational changes, deformation of the DNA helical structure, and formation of an asymmetric tetrameric complex. Based on these findings, we suggest a model for p53's Lys120 acetylation-dependent DNA-binding mode.


Assuntos
Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Sítios de Ligação/genética , Modelos Moleculares , Conformação Molecular , Ligação Proteica/genética , Elementos de Resposta/genética
9.
Chembiochem ; 17(11): 1008-11, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27120490

RESUMO

We describe a new expression system for efficient non-canonical amino acid mutagenesis in cultured mammalian cells by using the pyrrolysine tRNA synthetase/tRNACUA (Pyl) pair. A significant improvement in the incorporation of non-canonical amino acids into proteins was obtained by combining all the required genetic components into a single and compact vector that can be efficiently delivered to different mammalian cell lines by conventional transfection reagents.


Assuntos
Aminoácidos/metabolismo , Plasmídeos/metabolismo , Acetilação , Aminoacil-tRNA Sintetases/metabolismo , Animais , Código Genético , Células HCT116 , Células HEK293 , Humanos , Lisina/análogos & derivados , Lisina/metabolismo , Camundongos , Mutagênese , Células NIH 3T3 , Plasmídeos/genética , Engenharia de Proteínas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
10.
Lasers Med Sci ; 29(2): 855-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23529372

RESUMO

Facial scars in children have a profound psychosocial impact and require early and aggressive treatment. In this age group in particular, however, attention must be placed on the methodology so as not to trigger additional trauma-whether physical or emotional-as a sequela to the treatment. We assess the safety and efficacy of fractional CO2 in a prospective study of pediatric facial scars from various etiologies. Twenty four children, age 2-16 years, underwent fractional CO2 laser resurfacing. Recovery, clinical response, and adverse events were monitored at 3 days, 1 week, 1 month, 2 months, and 6 months. Photographs taken before treatment and 2 months after final treatment were independently evaluated and scored by two physicians. All patients tolerated treatment well, with minimal erythema an edema. The clinical improvement was scored as excellent in 14 patients (58%), good in 7 (29%), and fair in 3 (13%). No cases were graded as poor or worse. No adverse events were noted. The study supports the use of fractional CO2 resurfacing of pediatric facial scars as well tolerated and effective. Given the particularly rapid healing and clinical improvement of pediatric skin, fractional CO2 treatment should be offered early to mitigate both the physical and psychosocial stigmata of scars as early as possible.


Assuntos
Cicatriz/radioterapia , Lasers de Gás/uso terapêutico , Adolescente , Criança , Pré-Escolar , Cicatriz/patologia , Eritema/etiologia , Face/patologia , Humanos , Lasers de Gás/efeitos adversos , Resultado do Tratamento
11.
Mater Sci Eng C Mater Biol Appl ; 33(2): 923-31, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25427507

RESUMO

Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy.


Assuntos
Albuminas/química , Neoplasias do Colo/química , Corantes Fluorescentes/química , Nanopartículas/química , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Embrião de Galinha , Galinhas , Neoplasias do Colo/metabolismo , Corantes Fluorescentes/metabolismo , Humanos , Masculino , Nanopartículas/metabolismo , Tamanho da Partícula , Ratos
12.
Clin Exp Rheumatol ; 30(6 Suppl 74): 39-43, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23191939

RESUMO

UNLABELLED: Fibromyalgia represents the tip of the iceberg of chronic pain in the general population. We have attempted to estimate the prevalence of fibromyalgia in the Israeli population, using the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ), an instrument previously utilised in several European countries. METHODS: The LFESSQ-4 screens for widespread pain, and the LFESSQ-6 for widespread pain and chronic fatigue. The LFESSQ was administered via telephone to a sample of 1019 individuals. To estimate the positive predictive value (PPV) of LFESSQ-4 and LFESSQ-6, this questionnaire was submitted to a sample of rheumatology outpatients (n=76), who were examined to confirm or exclude fibromyalgia according to the 1990 criteria. The prevalence of fibromyalgia in the general population was estimated by applying the PPV to community subjects. RESULTS: In the community survey, 5.1% and 3.9% of individuals screened positive for the LFESSQ-4 and LFESSQ-6, respectively. The point prevalence of FMS in the Israeli general population was 2.6% (95%CI 1.7-3.4) when using LFESSQ-4 and 2.0% (95%CI 1.3-2.7) when using the LFESSQ-6 criteria. CONCLUSIONS: The prevalence of the fibromyalgia syndrome in the Israeli population is considerable and constitutes a significant health care issue. The prevalence is similar to that observed in other western populations. Based on this tool, over 25% of fibromyalgia cases appear to be among males, a proportion higher than generally appreciated.


Assuntos
Fibromialgia/diagnóstico , Fibromialgia/epidemiologia , Programas de Rastreamento/métodos , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Análise de Variância , Distribuição de Qui-Quadrado , Fadiga/diagnóstico , Fadiga/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/epidemiologia , Medição da Dor , Valor Preditivo dos Testes , Prevalência , Adulto Jovem
13.
J Nanobiotechnology ; 10: 36, 2012 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-22891637

RESUMO

BACKGROUND: The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. METHODS: The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. RESULTS AND DISCUSSION: Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. CONCLUSIONS: These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon cancer and others.


Assuntos
Neoplasias do Colo/diagnóstico , Corantes Fluorescentes/química , Nanopartículas/química , Albumina Sérica/química , Animais , Anticorpos Monoclonais/metabolismo , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/química , Neoplasias do Colo/metabolismo , Corantes Fluorescentes/metabolismo , Glicoproteínas/metabolismo , Histocitoquímica , Humanos , Secreções Intestinais , Teste de Materiais , Camundongos , Microscopia de Fluorescência , Modelos Biológicos , Aglutinina de Amendoim/metabolismo
14.
J Neurol ; 259(12): 2590-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22638565

RESUMO

Mutations in the potassium channel-related gene KCTD7 were described so far in a single family with progressive myoclonus epilepsy. We describe a unique phenotype: acute onset of myoclonus and ataxia, associated with abnormal opsoclonus-like eye movements; improvement of clinical symptoms under steroid treatment; and appearance of epileptic activity on EEG 2 years later without overt seizures. After excluding possible genetic causes, whole-genome exome sequencing was performed in order to identify the causative gene. One heterozygous missense mutation (R84W) was detected by exome sequencing and a large heterozygous deletion of exons 3 and 4 by MLPA analysis. The father is heterozygous for the R84W mutation and the mother is heterozygous for the exon 3+4 deletion. The mutation affects a highly conserved segment of the predicted protein, changing a basic amino acid into neutral. The large deletion probably results in a truncated protein. The different phenotype broadens the spectrum of KCTD7-related diseases. Therefore, patients diagnosed as having opsoclonus-myoclonus with an atypical course should be evaluated for KCTD7 mutations.


Assuntos
Deleção de Genes , Mutação de Sentido Incorreto/genética , Síndrome de Opsoclonia-Mioclonia/diagnóstico , Síndrome de Opsoclonia-Mioclonia/genética , Canais de Potássio/genética , Sequência de Aminoácidos , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Linhagem
15.
Clin Immunol ; 140(3): 284-90, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21624848

RESUMO

The relative frequency of the different forms of SCID may vary in different countries. The most frequent form in Israel is the autosomal-recessive T-B- SCID or Omenn syndrome while X-linked SCID is rare. We report our immunological and genetic analyses in multicentre study of patients presenting with either T-B- SCID or Omenn syndrome. Among 16 patients, we identified 7 novel mutations in 6 patients. In the RAG1 gene we detected two novel mutations: L454Q and 469 fs-4bpdel. In the RAG 2 gene: 3 novel mutations: D65Y, G157V, and E480X. One T-B- SCID patient was found to be a compound heterozygote for new mutations in the ADA gene: W264X and R235W. Prenatal diagnosis was performed in 8 families while others refused due to religious reasons. Identification of the new mutations expands our knowledge regarding the unique features of SCID phenotype in Israel and may help the families seeking for genetic counseling.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Homeodomínio/genética , Mutação , Proteínas Nucleares/genética , Imunodeficiência Combinada Severa/genética , Árabes/genética , Transplante de Medula Óssea , Feminino , Humanos , Recém-Nascido , Israel , Judeus/genética , Masculino , Gravidez , Diagnóstico Pré-Natal , Imunodeficiência Combinada Severa/terapia
16.
Eur J Hum Genet ; 19(3): 287-92, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21102625

RESUMO

Aicardi-Goutiéres syndrome (AGS) is a genetic neurodegenerative disorder with clinical symptoms mimicking a congenital viral infection. Five causative genes have been described: three prime repair exonuclease1 (TREX1), ribonucleases H2A, B and C, and most recently SAM domain and HD domain 1 (SAMHD1). We performed a detailed clinical and molecular characterization of a family with autosomal recessive neurodegenerative disorder showing white matter destruction and calcifications, presenting in utero and associated with multiple mtDNA deletions. A muscle biopsy was normal and did not show any evidence of respiratory chain dysfunction. Southern blot analysis of tissue from a living child and affected fetuses demonstrated multiple mtDNA deletions. Molecular analysis of genes involved in mtDNA synthesis and maintenance (POLGα, POLGß, Twinkle, ANT1, TK2, SUCLA1 and DGOUK) revealed normal sequences. Sequencing of TREX1 and ribonucleases H2A, B and C failed to reveal any mutations. Whole-genome homozygosity mapping revealed a candidate region containing the SAMHD1 gene. Sequencing of the gene in the affected child and two affected fetuses revealed a large deletion (9 kb), spanning the promoter, exon1 and intron 1. The parents were found to be heterozygous for this deletion. The identification of a homozygous large deletion in the SAMHD1 gene causing atypical AGS with multiple mtDNA deletions may add information regarding the involvement of mitochondria in self-activation of innate immunity by cell intrinsic components.


Assuntos
DNA Mitocondrial/genética , Deleção de Genes , Proteínas Monoméricas de Ligação ao GTP/genética , Doenças Autoimunes do Sistema Nervoso/genética , Southern Blotting , Feminino , Heterozigoto , Homozigoto , Humanos , Lactente , Masculino , Mitocôndrias/química , Mitocôndrias/genética , Malformações do Sistema Nervoso/genética , Linhagem , Gravidez , Proteína 1 com Domínio SAM e Domínio HD
17.
Mol Genet Metab ; 100(1): 65-70, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20202874

RESUMO

Leigh syndrome can be caused by defects in both nuclear and mitochondrial genes involved in energy metabolism. Recently, an increasing number of mutations in mitochondrial DNA encoding regions, especially in NADH dehydrogenase (respiratory chain complex I) subunits, have been reported as causative of early onset Leigh syndrome. We describe a patient whose fetal brain ultrasound demonstrated periventricular pseudocyst suggestive of a possible mitochondrial disorder who presented postnatally with Leigh syndrome. A muscle biopsy demonstrated a partial decrease in complex I and pyruvate dehydrogenase (PDH-E1 alpha) activity. Sequencing of the PDH-E1 alpha gene did not reveal any mutation. Sequencing of the mtDNA revealed a novel heteroplasmic G10254A (D66N) mutation in the ND3 gene. This change results in a substitution of aspartic acid to asparagine in a highly conserved domain of the ND3 subunit. The mutation could not be detected in the mother's blood or urine sediment. Blue native gel electrophoresis of muscle mitochondria revealed a normal size, albeit a decreased level of complex I. The G10254A substitution in the mtDNA-ND3 gene is another cause of maternally inherited Leigh syndrome. This case demonstrates that periventricular pseudocysts may be the initial in utero presentation in patients with mitochondrial disorders. We emphasize the importance of screening the mtDNA in pediatric patients as the first step in molecular diagnosis of Leigh syndrome.


Assuntos
DNA Mitocondrial/genética , Complexo I de Transporte de Elétrons/genética , Sequência de Aminoácidos , Evolução Fatal , Humanos , Lactente , Doença de Leigh/genética , Masculino , Mutação de Sentido Incorreto , Alinhamento de Sequência , Ultrassonografia Pré-Natal
18.
Can J Plast Surg ; 18(3): e33-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21886431

RESUMO

BACKGROUND: The burn eschar serves as a medium for bacterial growth and a source of local and systemic infection. To prevent or minimize these complications, it is important to debride the eschar as early as possible. OBJECTIVE: To identify the presence of viable skin within the excisions by examining tangentially excised burn eschars. METHODS: A total of 146 samples of burned human tissue were removed during 54 routine sharp tangential excision procedures (using dermatomes). The samples were histologically examined to identify the relative thickness of the dead, intermediate and viable layers. RESULTS: The mean (± SD) thickness of the excised samples was 1.7±1.1 mm. The sacrificed viable tissue (mean thickness 0.7±0.8 mm) occupied 41.2% of the entire thickness of the excision. In 32 biopsies (21.8%; 95% CI 16.0 to 29.3), the excision did not reach viable skin. Only eight biopsies (5.4%; 95% CI 2.8 to 10.1) contained all of the necrotic tissue without removing viable tissue. CONCLUSIONS: The thickness of a single tangentially excised layer of eschar is not much greater than the actual thickness of the entire skin and often contains viable tissue. Because surgical debridement is insufficiently selective, more selective means of debriding burn eschars should be explored.

19.
World J Surg Oncol ; 6: 28, 2008 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-18312655

RESUMO

BACKGROUND: Antecedent trauma has been implicated in the causation of soft tissue tumors. Several criteria have been established to define a cause-and-effect relationship. We postulate possible mechanisms in the genesis of soft tissue tumors following antecedent traumatic injury. CASE PRESENTATION: We present a 27-year-old woman with a paraspinal desmoid tumor, diagnosed 3-years following a motor vehicle accident. Literature is reviewed. CONCLUSION: Soft tissue tumors arising at the site of previous trauma may be desmoids, pseudolipomas or rarely, other soft tissue growths. The cause-and-effect issue of desmoid or other soft tissue tumors goes beyond their diagnosis and treatment. Surgeons should be acquainted with this diagnostic entity as it may also involve questions of longer follow-up and compensation and disability privileges.


Assuntos
Fibromatose Agressiva/etiologia , Neoplasias Pós-Traumáticas/etiologia , Lesões dos Tecidos Moles/complicações , Neoplasias de Tecidos Moles/etiologia , Neoplasias da Coluna Vertebral/etiologia , Adulto , Feminino , Fibromatose Agressiva/cirurgia , Humanos , Imageamento por Ressonância Magnética , Neoplasias Pós-Traumáticas/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias da Coluna Vertebral/cirurgia
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