ABSTRACT
Purpouse: One Step Nucleic Acid Amplification (OSNA) has been previously proposed for the diagnosis of lymph node metastases (LNMs) from several malignant conditions by quantifying the ...number of copies of cytokeratin 19 mRNA. Our aim was to evaluate the results obtained by OSNA in the lymph nodes of patients with papillary thyroid carcinoma (PTC) by comparing our results with the findings observed using standard pathological examination. Materials and Methods: Fifty human lymph nodes (from five patients with diagnosed PTC) were studied. Each node was divided into two: one half was used for molecular study ("OSNA-node"), and the other half was used for conventional staining with hematoxylin and eosin ("HE-non-OSNA node"). Three cytological imprints using Papanicolaou and May-Grunwald-Giemsa strains were obtained from both node halves. The results from each technique were compared, and ROC analysis was performed. Results: The OSNA study showed 22 positive samples for LNM (44%), which demonstrate a high concordance rate with the results observed using conventional pathological examination (cytology of "OSNA-node" and HE of "Non-OSNA node") with specificity and sensitivity values greater than 86% and 89%, respectively. However, both comparisons differed in the number of copies of mRNA as the best cut-off (260 copies in the first case and 93 in the second case). Conclusions: The OSNA results for the detection of LNM in patients with PTC are comparable with those observed using conventional techniques. However, its quantitative nature could be useful to more accurately detect lymph node involvement.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: We determined the effect of detecting ectopic thymic tissue in thymectomy specimens on the long-term outcome of patients with myasthenia gravis. Methods: A total of 83 consecutive patients ...with generalized seropositive nonthymomatous myasthenia gravis underwent transsternal extended thymectomy (T-3b according to Myasthenia Gravis Foundation of America). Ectopic thymic tissue was only accepted when Hassal’s corpuscles in the excised cervicomediastinal fat were documented. The primary endpoint was to assess differences in time to obtain complete stable remission (CSR) according to the presence or absence of ectopic thymus. Results: Thirty-five patients (42.2%) had ectopic thymic tissue. The mean follow-up was 88.4 ± 36.3 months (range 20–144). By the Kaplan–Meier analysis method, the estimated median follow-up to obtain a CSR in the group without ectopic thymic tissue was 32.9 months (95% confidence interval CI 21.1–44.8 months) and 117.8 months (95% CI 98.0–137.6 months) for the group with ectopic thymic tissue (log-rank test, p = 0.0002). The probability over time of obtaining CSR for the groups without and with ectopic thymic tissue was 65% vs 26% at 5 years. After stratification by hyperplasia or involution of the thymus as well as by post-thymectomy immunomodulating regimen (prednisone and prednisone–tacrolimus), the probability over time of obtaining CSR at 5 years was also significantly higher for patients without ectopic thymic tissue than for those with ectopic thymic tissue. Conclusions: The clinical outcome of patients with nonthymomatous seropositive myasthenia gravis is significantly affected by the presence of ectopic thymic tissue in the mediastinal fat.
A mutation in the HERC2 gene has been linked to a severe neurodevelopmental disorder with similarities to the Angelman syndrome. This gene codifies a protein with ubiquitin ligase activity that ...regulates the activity of tumor protein p53 and is involved in important cellular processes such as DNA repair, cell cycle, cancer, and iron metabolism. Despite the critical role of HERC2 in these physiological and pathological processes, little is known about its relevance in vivo. Here, we described a mouse with targeted inactivation of the Herc2 gene. Homozygous mice were not viable. Distinct from other ubiquitin ligases that interact with p53, such as MDM2 or MDM4, p53 depletion did not rescue the lethality of homozygous mice. The HERC2 protein levels were reduced by approximately one-half in heterozygous mice. Consequently, HERC2 activities, including ubiquitin ligase and stimulation of p53 activity, were lower in heterozygous mice. A decrease in HERC2 activities was also observed in human skin fibroblasts from individuals with an Angelman-like syndrome that express an unstable mutant protein of HERC2. Behavioural analysis of heterozygous mice identified an impaired motor synchronization with normal neuromuscular function. This effect was not observed in p53 knockout mice, indicating that a mechanism independent of p53 activity is involved. Morphological analysis showed the presence of HERC2 in Purkinje cells and a specific loss of these neurons in the cerebella of heterozygous mice. In these animals, an increase of autophagosomes and lysosomes was observed. Our findings establish a crucial role of HERC2 in embryonic development and motor coordination.
A mutation in the HERC2 gene has been linked to a severe neurodevelopmental disorder with similarities to the Angelman syndrome. This gene codifies a protein with ubiquitin ligase activity that ...regulates the activity of tumor protein p53 and is involved in important cellular processes such as DNA repair, cell cycle, cancer, and iron metabolism. Despite the critical role of HERC2 in these physiological and pathological processes, little is known about its relevance in vivo. Here, we described a mouse with targeted inactivation of the Herc2 gene. Homozygous mice were not viable. Distinct from other ubiquitin ligases that interact with p53, such as MDM2 or MDM4, p53 depletion did not rescue the lethality of homozygous mice. The HERC2 protein levels were reduced by approximately one-half in heterozygous mice. Consequently, HERC2 activities, including ubiquitin ligase and stimulation of p53 activity, were lower in heterozygous mice. A decrease in HERC2 activities was also observed in human skin fibroblasts from individuals with an Angelman-like syndrome that express an unstable mutant protein of HERC2. Behavioural analysis of heterozygous mice identified an impaired motor synchronization with normal neuromuscular function. This effect was not observed in p53 knockout mice, indicating that a mechanism independent of p53 activity is involved. Morphological analysis showed the presence of HERC2 in Purkinje cells and a specific loss of these neurons in the cerebella of heterozygous mice. In these animals, an increase of autophagosomes and lysosomes was observed. Our findings establish a crucial role of HERC2 in embryonic development and motor coordination.
A mutation in the HERC2 gene has been linked to a severe neurodevelopmental disorder with similarities to the Angelman syndrome. This gene codifies a protein with ubiquitin ligase activity that ...regulates the activity of tumor protein p53 and is involved in important cellular processes such as DNA repair, cell cycle, cancer, and iron metabolism. Despite the critical role of HERC2 in these physiological and pathological processes, little is known about its relevance in vivo. Here, we described a mouse with targeted inactivation of the Herc2 gene. Homozygous mice were not viable. Distinct from other ubiquitin ligases that interact with p53, such as MDM2 or MDM4, p53 depletion did not rescue the lethality of homozygous mice. The HERC2 protein levels were reduced by approximately one-half in heterozygous mice. Consequently, HERC2 activities, including ubiquitin ligase and stimulation of p53 activity, were lower in heterozygous mice. A decrease in HERC2 activities was also observed in human skin fibroblasts from individuals with an Angelman-like syndrome that express an unstable mutant protein of HERC2. Behavioural analysis of heterozygous mice identified an impaired motor synchronization with normal neuromuscular function. This effect was not observed in p53 knockout mice, indicating that a mechanism independent of p53 activity is involved. Morphological analysis showed the presence of HERC2 in Purkinje cells and a specific loss of these neurons in the cerebella of heterozygous mice. In these animals, an increase of autophagosomes and lysosomes was observed. Our findings establish a crucial role of HERC2 in embryonic development and motor coordination.
This short letter is in response to the article published in your
publication about single-incision laparoscopic bariatric surgery, by
Chih-Kun Huang. We want to focus on the technical aspects.
Objective: A single-centre, non-randomized, non-controlled study was designed to compare the long-term post-thymectomy clinical outcome in anti-AChR-positive, anti-AChR-negative and ...anti-MuSK-positive patients with non-thymomatous myasthenia gravis (MG). Methods: A total of 331 consecutive patients with seropositive MG, 55 with seronegative MG and 10 with anti-MuSK-positive MG underwent extended transsternal thymectomy (T-3b according to Myasthenia Gravis Foundation of America). The primary endpoint was to assess differences in the rate of complete stable remission (CSR) in patients with and without anti-AChR and anti-MuSK antibodies. Results: The mean follow-up was 218.3 (SD 128.1) months in the seropositive MG group, 149.8 (SD 131.1) in the seronegative group and 169.9 (SD 116) in the anti-MuSK-positive group. In the seropositive MG group, the probability of obtaining CSR at 5 years post-thymectomy was 51.1% for the seropositive group compared with 40 for the seronegative group (p = 0.05) and 20 for the anti-MuSK-positive group (p = 0.03). Differences between the seronegative and anti-MuSK-positive groups were not observed. The estimated median follow-up to obtain a CSR was 17.8 months (95% confidence interval CI 15.7 - 19.8 months) in seropositive MG patients, 22.1 (95% CI 16.7 - 27.4 months) in seronegative MG patients and 20.6 (95% CI 13.3 - 27.9 months) in anti-MuSK-positive MG patients (long-rank test, p = 0.07). Conclusions: Long-term post- thymectomy clinical outcome was better in patients with conventional anti-AChR antibodies than in those with seronegative disease. In seronegative anti-MuSK-positive MG, thymectomy seems to be less effective than in anti-MuSK-negative MG but this study cannot answer the question of whether thymectomy should be undertaken in anti-MuSK-positive patients.
Background: Numerous studies have shown an increase in the incidence of thyroid cancer (TC) in recent years. Objectives: In this paper, we reviewed the incidence of TC in a series of patients ...undergoing thyroid surgery at a single institution over a 10-year period. Patients and Methods: The cohorts were divided into two periods (2001-2005 and 2006-2010) with the purpose of comparing various clinicopathologic variables. Results: A total of 1,263 patients were included. A significant increase in the number of malignancies was shown in the second period, namely 90 cases in 2001-2005 (15.2% of all interventions) compared to 163 cases in 2006-2010 (24.3%) (p < 0.001). These differences were attributed to an increase in papillary thyroid carcinoma (PTC), as there were 66 PTC cases in the first period (11.13% of thyroidectomies performed) compared to 129 cases in the second period (19.25%). There were no clinicohistological differences among PTC cases in these two periods. Conclusions: Over the last decade, there has been an increase in the incidence of TC in patients undergoing thyroid surgery. This increase is exclusively due to increases in PTC. Our study verifies the existence of this trend in our geographical area, similar to that noted in other parts of the world.
Resumen Introducción y objetivos Algunas medidas antropométricas muestran mayor capacidad que otras para discriminar la presencia de factores de riesgo cardiovascular. Este trabajo estima la magnitud ...de la asociación de diversos indicadores antropométricos de obesidad con hipertensión, dislipemia y prediabetes (glucemia basal o glucohemoglobina alteradas). Métodos Análisis transversal de la información recogida en 2.022 sujetos del estudio PREDAPS (etapa basal). Se definió obesidad general como índice de masa corporal ≥ 30 kg/m2 y obesidad abdominal con 2 criterios: a) perímetro de cintura (PC) ≥ 102 cm en varones/PC ≥ 88 cm en mujeres, y b) índice cintura/estatura (ICE) ≥ 0,55. La magnitud de la asociación se estimó mediante regresión logística. Resultados La hipertensión arterial mostró la asociación más alta con la obesidad general en mujeres (OR = 3,01; IC95%, 2,24-4,04) y con la obesidad abdominal según el criterio del ICE en varones (OR = 3,65; IC95%, 2,66-5,01). La hipertrigliceridemia y los valores bajos de colesterol unido a lipoproteínas de alta densidad mostraron la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,49; IC95%, 1,68-3,67 y OR = 2,70; IC95%, 1,89-3,86) y la obesidad general en varones (OR = 2,06; IC95%, 1,56-2,73 y OR = 1,68; IC95%, 1,21-2,33). La prediabetes mostró la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,48; IC95%, 1,85-3,33) y con obesidad abdominal según el criterio del PC en varones (OR = 2,33; IC95%, 1,75-3,08). Conclusiones Los indicadores de obesidad abdominal mostraron la mayor asociación con la presencia de prediabetes. La relación de los indicadores antropométricos con hipertensión y con dislipemia mostró resultados heterogéneos.
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