Publications

Molecular fusion events have a prominent role in the initial steps of carcinogenesis. In this study, a bioinformatics analysis was performed between four organisms that are known to induce cancer development in humans: two viruses, Human Herpesvirus 4, and Human T-cell leukaemia virus, one bacterium, Helicobacter Pylori, and one trematode, Schistosoma mansoni. The annotated proteomes from these organisms were analysed using the SAFE software to identify protein fusion events, which may provide insight into protein function similarities and possible merging events during the course of evolution. Based on the results, five fused proteins with very similar functions were detected, whereas proteins with different functions that might act in the same molecular complex or biochemical pathway were not found. Thus, this study analysed the above four well-known cancer-related organisms with de novo bioinformatics programs and provided useful information on protein fusion events, hopefully leading to deeper understanding of carcinogenenesis.

Normal menopause is associated with vascular endothelial dysfunction, an early stage of atherosclerosis. The effect of premature ovarian failure (or premature menopause) on endothelial function in young women is unknown. Endothelial function was assessed in 18 women with premature ovarian failure before and after 6 months of hormone therapy and was compared with the endothelial function of 20 age- and body mass index-matched premenopausal women. Brachial artery diameter was measured both during hyperemia (an index of endothelium-dependent vasodilation) and in response to glyceryl trinitrate (an index of endothelium-independent vaso-dilation). Flow-mediated dilation was significantly lower in women with premature ovarian failure at baseline (increase in brachial artery diameter during hyperemia by 3.06 ± 4.33%) than in control women (increase by 8.84 ± 2.15%; P < 0.0005). Glyceryl trinitrate-induced vasodilation did not differ between the groups. After hormone therapy for 6 months, flow-mediated dilation was improved in women with premature ovarian failure, increasing by more than 2-fold (7.41 ± 3.86%; P < 0.005 compared with pretreatment) and reaching normal values (P not significant compared with control women). Glyceryl trinitrate-induced vasodilation did not change after treatment in women with premature ovarian failure. Young women with premature ovarian failure have significant vascular endothelial dysfunction. Early onset of endothelial dysfunction associated with sex steroid deficiency may contribute to the increased risk of cardiovascular disease and mortality in young women with premature ovarian failure. Hormone therapy restores endothelial function within 6 months of treatment.

Glucocorticoids continue to be the major immunomodulatory agents used in clinical medicine today. However, their actions as anti-inflammatory and immunosuppressive drugs are both beneficial and deleterious. We analyzed the effect of glucocorticoids on the gene expression profile of peripheral blood mononuclear cells from healthy donors. DNA microarray analysis combined with quantitative TaqMan PCR and flow cytometry revealed that glucocorticoids induced the expression of chemokine, cytokine, and complement family members as well as of newly discovered innate immune-related genes, including scavenger and Toll-like receptors. In contrast, glucocorticoids repressed the expression of adaptive immune-related genes. Simultaneous inhibitory and stimulatory effects of glucocorticoids were found on inflammatory T helper subsets and apoptosis-related gene clusters. In cells activated by T cell receptor cross-linking, glucocorticoids down-regulated the expression of specific genes that were previously up-regulated in resting cells, suggesting a potential new mechanism by which they exert positive and negative effects. Considering the broad and continuously renewed interest in glucocorticoid therapy, the profiles we describe here will be useful in designing more specific and efficient treatment strategies.

Background: A strong genetic background and gender are believed to be involved in thyroid autoimmunity (TA). The age these factors become manifest is less clear, however. The objective of the present study was to determine the prevalence of TA in children and adolescents and to determine if there are relationships between the period of onset of TA and gender and between TA and maternal autoimmunity. Methods: Antithyroperoxidase antibodies (anti-TPO Ab), antithyroglobulin antibodies (anti-Tg Ab), thyrotropin, thyroxine, triiodothyronine, and urinary iodine were determined in 440 healthy schoolchildren (200 boys and 240 girls), aged 5–18 years, and in 123 mothers living in an iodine-replete region. Results: The prevalence of positive anti-TPO and anti-Tg Ab was 4.6% and 4.3%, respectively. In girls, the prevalence of positive anti-TPO Ab was higher in Tanner stage II–V compared to Tanner stage I (8.2% vs. 2.2%; p < 0.05). No difference was detected with regard to anti-Tg Ab. In girls, positive anti-TPO and anti-Tg Ab levels were associated with significantly greater thyroid volume. Hypoechogenicity was detected in 52.6% and 36.8% of the children with positive anti-TPO or anti-Tg Ab, respectively (p = 0.0005). The prevalence of autoimmune thyroiditis, as defined by positive serum anti-TPO and/or anti-Tg and an echographic pattern of the thyroid gland having diffuse or irregular hypoechogenicity, was 2.5%. Mothers of anti-TPO Ab positive children had positive anti-TPO Ab more frequently compared to mothers of anti-TPO Ab negative children (82% vs. 18%; p = 0.0005). Mothers of anti-Tg Ab positive children had positive anti-Tg Ab more frequently compared to mothers of anti-Tg Ab negative children (75% vs. 25%; p = 0.0005). Conclusions: These findings demonstrate that thyroid antibody positivity in children was significantly associated with maternal autoimmunity and their development in girls emerges at puberty. Since heredity, female gender, and puberty are strongly associated with TA, girls in families with TA should be examined at the onset of puberty.

In obese adults, sleep apnea is associated with excessive daytime sleepiness (EDS) and cardiometabolic risk factors. In children, on the other hand, sleep-disordered breathing (SDB) is primarily associated with anatomic abnormalities and neurocognitive impairment, whereas studies on potential concurrent metabolic aberrations and EDS have been limited and inconsistent. In this study, we examined the joint effect of SDB and obesity in EDS as well as proinflammatory and metabolic markers.One hundred fifty children, aged 5-17 yr, were consecutively recruited from our sleep disorders clinic and a subset of the Penn State Children's Cohort. Every child had a thorough history and physical examination, 9-h polysomnographic study, and a single blood draw for the assessment of IL-6, TNFalpha, soluble IL-6 receptor, TNF receptor-1, hypersensitive C-reactive protein, leptin, and adiponectin. In addition, parents completed a subjective questionnaire to assess EDS. Analysis of covariance was performed on four groups that were separated by SDB severity and body mass index.EDS frequency increased progressively and significantly in the four groups. There was a significant linear trend in plasma IL-6, TNF receptor-1, hypersensitive C-reactive protein, and leptin concentrations, with lowest levels observed in lean controls and highest in overweight/obese with moderate SDB. Adiponectin followed the opposite pattern.This study suggests that in a clinical sample of obese children, SDB is associated with EDS, elevation of proinflammatory cytokines, increased leptin, and decreased adiponectin. All these changes point to an inflammatory/insulin resistance state, suggesting that SDB in obese children share many similarities with SDB in obese adults.

Many people are worried about their social appearance. The fear of negative evaluation and judgment regarding one's look in social circumstances is referred to as social appearance anxiety. Social appearance anxiety belongs to social anxiety. The aim of the present study was to validate the Social Appearance Anxiety Scale (SAAS) in the Greek language and to examine its psychometric properties. An online survey was conducted in a Greek population sample of adolescents and young adults aged 18 to 35 years. The survey instruments included the Social Appearance Anxiety Scale, the Social Physique Anxiety Scale (SPAS), 2 subscales of Multidimensional Body-Self Relations Questionnaire Appearance Scale (MBSRQ), the Appearance Schemas Inventory-Revised Scale (ASI-R) and the Depression Anxiety Stress Scale (DASS). A total of 429 respondents participated in this research. The statistical analysis showed that the Greek version of the SAAS has good psychometric properties. The internal consistency of questions within the SAAS was 0.942. Positive correlations were found between SAAS and SPAS, the overweight preoccupation subscale of MBSRQ, the ASI-R and the DASS, while negative correlations were observed between SAAS and the appearance evaluation subscale of MBSRQ and age. The results of this study suggest that the Greek version of SAAS can be used as a reliable and valid instrument in the Greek population.

Our purpose was to describe the hypoplastic or plexiform inferior petrosal sinus as a potential cause of false-negative sampling results in patients with Cushing’s disease. Five hundred and one patients with surgically proven Cushing’s disease and negative or equivocal magnetic resonance imaging scans of the pituitary gland underwent petrosal sinus sampling. Four patients (0.8%) with surgically proven Cushing’s disease had false-negative results of petrosal sinus sampling. Retrograde inferior petrosal sinograms in these patients were reviewed to evaluate the anatomy of the inferior petrosal sinuses for abnormalities that could have contributed to this misdiagnosis. In addition, the retrograde inferior petrosal sinograms of 100 consecutive patients were reviewed to establish the frequency of asymmetric and/or hypoplastic inferior petrosal sinuses. All four patients with false-negative results of petrosal sampling demonstrated a hypoplastic or plexiform inferior petrosal sinus ipsilateral to an ACTH-secreting microadenoma. When the sampling catheter was in the hypoplastic petrosal sinus, retrograde sinograms from the contralateral side demonstrated anomalous drainage patterns on the side of the hypoplastic sinus. Because the negative results of petrosal sinus sampling false-suggested the presence of the ectopic ACTH syndrome, curative transsphenoidal surgery in these four patients was delayed up to 31 months. We conclude that the presence of a unilateral hypoplastic or plexiform inferior petrosal sinus can result in anomalous drainage from the pituitary gland that may lead to false-negative sampling results in patients with Cushing’s disease.

No abstract is provided for this article.

Introduction: Primary aldosteronism (PA), the most common endocrine cause of secondary hypertension, is generally under diagnosed using current diagnostic tests. Objective: To present our findings, based on studies using modified diagnostic tests, on the diagnosis, prevalence and treatment of PA. Design and Methods: We prospectively studied 992 hypertensive patients and 278 matched controls. Participants underwent conventional confirmatory tests for the diagnosis of PA modified by the addition of dexamethasone including the Fludrocortisone Dexamethasone Suppression Test (FDST), the Dexamethasone Captopril Valsartan Test (DCVT) and the Dexamethasone Saline Infusion Test (DSIT). Normal cut-offs of basal aldosterone-to-renin ratio and post-test (FDST, DCVT and DSIT) aldosterone levels and aldosterone-to-renin ratio were calculated from the control groups, who had normal adrenal imaging. Results: Hypertensive patients had significantly higher baseline blood pressure and lower serum potassium levels compared to controls. Using the basal aldosterone-to-renin ratio as screening test, the prevalence of PA was 17.8%. After applying the modified tests to all patients, the prevalence of PA was 33.4%. Targeted treatment with Mineralocorticoid Receptor Antagonists was administered in 252 hypertensives, with bilateral PA; 188 (74.6%) of them obtained a biochemical response and normalization of blood pressure. Unilateral disease had 48 patients who underwent laparoscopic adrenalectomy obtaining a biochemical success rate was 94%. Conclusion: Our modified methodology and the use of normotensive controls for calculation of normal cut-offs of aldosterone suppression, significantly improves the sensitivity and specificity of the existing tests on the diagnosis of PA, allowing the detection of milder forms.

Cortisol, a key mediator of the stress response, has been associated with obesity and metabolic syndrome manifestations as early as in childhood. Scalp hair cortisol has been proposed as a reliable index of long-term circulating cortisol. We aimed to investigate whether obese prepubertal girls have higher scalp hair cortisol than normal-weight controls and whether hair cortisol levels are correlated with salivary cortisol concentrations in these groups. In this cross-sectional study, 25 obese girls and 25 normal-weighted, age-matched girls were enrolled. Anthropometric evaluation, blood chemistry and salivary cortisol measurements were performed, and body mass index (BMI) and areas under the curve with respect to ground (AUCg) were calculated. Hair cortisol determination was performed with liquid chromatography-tandem mass spectrometry. Both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p < .001 and p = .002, respectively). A positive correlation between hair cortisol and BMI Z-score was found (rho = .327, p = .025), while hair cortisol correlated positively with salivary cortisol AUCg (rho = .3, p = .048). We conclude that obese prepubertal girls have higher hair and salivary cortisol concentrations than their age-matched lean counterparts. Hair cortisol assessment seems to be a sensitive method of evaluating systemic cortisol exposure, which is supported by our finding that hair cortisol is associated with salivary concentrations of the hormone. Lay Summary: Cortisol is the key hormone of the stress response. Childhood obesity has been associated with cortisol production dysregulation. Our findings suggest a positive association between obesity in prepubertal girls and elevated cortisol concentrations, measured in saliva and hair.