201 research outputs found

    Axillary node metastasis from differentiated thyroid carcinoma with hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings

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    <p>Abstract</p> <p>Background</p> <p>Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis.</p> <p>Case presentation</p> <p>Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hürthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml.</p> <p>Discussion and Conclusion</p> <p>Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.</p

    Adolescent Self-Organization and Adult Smoking and Drinking over Fifty Years of Follow-Up:The British 1946 Birth Cohort

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    Variations in markers of adolescent self-organization predict a range of economic and health-related outcomes in general population studies. Using a population-based birth cohort study we investigated associations between adolescent self-organization and two common factors over adulthood influencing health, smoking and alcohol consumption. The MRC National Survey of Health and Development (the British 1946 birth cohort) was used to test associations between a dimensional measure of adolescent self-organization derived from teacher ratings, and summary longitudinal measures of smoking and alcohol consumption over the ensuing five decades. Multinomial regression models were adjusted for sex, adolescent emotional and conduct problems, occupational social class of origin, childhood cognition, educational attainment and adult occupational social class. With all covariates adjusted, higher adolescent self-organization was associated with fewer smoking pack years, although not with quitting; there was no association with alcohol consumption across adulthood (none or heavy compared with light to moderate). Adolescent self-organization appears to be protective against smoking, but not against heavy alcohol consumption. Interpretation of this differential effect should be embedded in an understanding of the social and sociodemographic context in which these health behaviours occur over time

    Interactions of polymorphisms in different clock genes associated with circadian phenotypes in humans

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    Several studies have shown that mutations and polymorphisms in clock genes are associated with abnormal circadian parameters in humans and also with more subtle non-pathological phenotypes like chronotypes. However, there have been conflicting results, and none of these studies analyzed the combined effects of more than one clock gene. Up to date, association studies in humans have focused on the analysis of only one clock gene per study. Since these genes encode proteins that physically interact with each other, combinations of polymorphisms in different clock genes could have a synergistic or an inhibitory effect upon circadian phenotypes. In the present study, we analyzed the combined effects of four polymorphisms in four clock genes (Per2, Per3, Clock and Bmal1) in people with extreme diurnal preferences (morning or evening). We found that a specific combination of polymorphisms in these genes is more frequent in people who have a morning preference for activity and there is a different combination in individuals with an evening preference for activity. Taken together, these results show that it is possible to detect clock gene interactions associated with human circadian phenotypes and bring an innovative idea of building a clock gene variation map that may be applied to human circadian biology

    Leishmania-Induced Inactivation of the Macrophage Transcription Factor AP-1 Is Mediated by the Parasite Metalloprotease GP63

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    Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity

    Post-exercise contractility, diastolic function, and pressure: Operator-independent sensor-based intelligent monitoring for heart failure telemedicine

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    <p>Abstract</p> <p>Background</p> <p>New sensors for intelligent remote monitoring of the heart should be developed. Recently, a cutaneous force-frequency relation recording system has been validated based on heart sound amplitude and timing variations at increasing heart rates.</p> <p>Aim</p> <p>To assess sensor-based post-exercise contractility, diastolic function and pressure in normal and diseased hearts as a model of a wireless telemedicine system.</p> <p>Methods</p> <p>We enrolled 150 patients and 22 controls referred for exercise-stress echocardiography, age 55 ± 18 years. The sensor was attached in the precordial region by an ECG electrode. Stress and recovery contractility were derived by first heart sound amplitude vibration changes; diastolic times were acquired continuously. Systemic pressure changes were quantitatively documented by second heart sound recording.</p> <p>Results</p> <p>Interpretable sensor recordings were obtained in all patients (feasibility = 100%). Post-exercise contractility overshoot (defined as increase > 10% of recovery contractility vs exercise value) was more frequent in patients than controls (27% vs 8%, p < 0.05). At 100 bpm stress heart rate, systolic/diastolic time ratio (normal, < 1) was > 1 in 20 patients and in none of the controls (p < 0.01); at recovery systolic/diastolic ratio was > 1 in only 3 patients (p < 0.01 vs stress). Post-exercise reduced arterial pressure was sensed.</p> <p>Conclusion</p> <p>Post-exercise contractility, diastolic time and pressure changes can be continuously measured by a cutaneous sensor. Heart disease affects not only exercise systolic performance, but also post-exercise recovery, diastolic time intervals and blood pressure changes – in our study, all of these were monitored by a non-invasive wearable sensor.</p
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