HIGH EXPRESSION OF CANCER TESTIS ANTIGENS MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, AND GAGE IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE LARYNX

Background. Despite diagnostic and therapeutic advances in head and neck cancer, the 5-year survival of patients with laryngeal cancer has not improved in the last 30 years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy. Methods. We evaluated by immunohistochemical analysis the expression of cancer testis antigens MAGE-A4 (57B), MAGE-C1 (CT7-33), MAGE-A1 (MA454), MAGE-A3 (M3H67), MAGE-C2 (CT10.5), NY-ESO-1 (E978), and GAGE (GAGE) in squamous cell carcinoma (SCC) of the larynx. Results. A total of 63 cases (57 men and 6 women) of laryngeal SCC were available for this study. The findings were correlated with the clinical course and laboratory data. Expression of at least 1 cancer testis antigen was detected in 42 of 63 of the laryngeal SCCs (67%). In 34 of 42 of the positive cases (81%) there was simultaneous expression of >= 2 cancer testis antigens. There was significant correlation between antigen expression and advanced tumor stage (stage III/IV) in cases with reactivity to only 1 antibody (p = .01) as well as in the cases with reactivity to >= 2 primary antibodies (>= 2 mAbs, p = .04). There was no association between survival and expression of any of the analyzed antigens. Conclusions. We find a high incidence of cancer testis antigen expression in SCCs of the larynx, which was correlated with advanced clinical stage. Our data indicate that cancer testis antigens could be valuable vaccine targets in laryngeal tumors, especially in those with a worse prognosis. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 702-707, 2011

Postnatal growth and cardiometabolic profile in young adults born large for gestational age

Context The association between large for gestational age (LGA) phenotype, postnatal growth and cardiometabolic risk (CMR) in adult life remains unclear. The role of IGF1 genotype on LGA-related outcomes in adult life is unknown. Aim To assess the postnatal growth, IGF-I levels, CMR and the influence of the 737.738 IGF1 in adults born LGA. Subjects Case-control study (n = 515) nested in a population-based prospective cohort (n = 2063); 117 LGA and 398 gender-matched controls appropriate for gestational age (AGA) subjects. Methods Anthropometry was evaluated at birth, at 9-10 and at 23-25 years old. At the age of 23-25 years, blood pressure (BP), glycaemia, insulinaemia, homeostasis model assessment - insulin resistance, lipids, fibrinogen, and plasma IGF-I and 737.738 IGF1 polymorphism were assessed. Results Large for gestational age subjects remained heavier and taller than AGA at 9-10 and 23-25 years (P < 0.05); at 23-25 years, LGA had greater waist circumference (WC; P < 0.05) and higher BP (P < 0.05) than controls. Body proportionality at birth did not predict metabolic outcome. LGA subjects presenting catch-down of weight in childhood had lower body mass index (BMI; P = 0.001), lower WC (P < 0.05) and lower BP (P < 0.05) at 2325 years. 737.738 IGF-I genotype differed between groups (P < 0.001). Homozygosis for polymorphic alleles was associated with increased odds of LGA (OR: 3.2; 95% CI: 1.5-6.9), higher IGF-I (56.9 +/- 16.4 vs 37.7 +/- 16.0 nm; P < 0.01) and lower BP (114/68 vs 121/73 mmHg; P < 0.05). Conclusions Young adults born LGA presented higher BMI, WC and BP and appear to be at higher CMR risk than AGA subjects. The 737.738 IGF1 polymorphism appears to play a role on birth size and LGA-related metabolic outcomes.

High prevalence of polycystic ovary syndrome in women born small for gestational age

There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA). This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirao Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS. The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups. The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age

Objective: To assess whether the -11391G > A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life. Design: Case-control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date. Methods: ADIPOQ -11391G > A genotype-phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8-10 years (catch-down growth), and at 23-25 years of age (cardiometabolic profile). Results: The -11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16-16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23-25 years, the -11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7 +/- 6.2 versus GA: 12.2 +/- 6.5 versus AA: 14.2 +/- 6.8 mu g/ml; P < 0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P < 0.001) at 23-25 years. Conclusions: The -11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.

Validation of a food frequency questionnaire for assessing dietary nutrients in Brazilian children 5 to 10 years of age

Objective: This study aimed to assess the relative validity of a food frequency questionnaire.(FFQ), previously validated to measure usual intakes in adults, for measuring dietary intakes in children 5 to 10 y of age. Methods: Dietary intakes were measured using an FFQ and a 3-d dietary record. Healthy children, 5 to 10 y old (n = 151), were recruited from public schools and asked to answer the questions in the FFQ and to provide non-consecutive 3-d dietary records based on reported estimated portion sizes. Paired sample t tests and Pearson`s correlation coefficients were conducted to determine whether the two instruments reported similar values for energy and nutrients. The agreement of quartile categorization between the two instruments was also examined. Results: Estimated energy and nutrient intakes derived from the FFQ were significantly higher than those derived from 3-d dietary records. As expected, Pearson`s correlations increased after adjusting for residual measurement error, presumably due to exclusion of the high within-person variability in intake of these nutrients. Moderate to high (r > 0.50) correlation coefficients were verified for some nutrients such as calcium, folate, vitamin 132, vitamin A, and vitamin C. Conclusion: This FFQ, originally developed for use in adults, appears to overestimate usual energy and nutrient intakes in children 5 to 10 y of age. Further work is necessary to conduct a calibration study to establish adequate portion sizes before instrument adoption in this population. (c) 2008 Elsevier Inc. All rights reserved.

Genetic associations between age at first calving and heifer body weight and scrotal circumference in Nelore cattle

P>Age at first calving (AFC) measures the entry of heifers into the beef cattle production system. This trait can be used as a selection criterion for earlier reproductive performance. Using data from Nelore cattle participating in the `Program for Genetic Improvement of the Nelore Breed` (PMGRN-Nelore Brazil), bi-trait analyses were performed using the restricted maximum likelihood method, based on an AFC animal model and the following traits: female body weight adjusted to 365 (BW365) and 450 (BW450) days of age, and male scrotal circumference adjusted to 365 (SC365), 450 (SC450), 550 (SC550) and 730 (SC730) days of age. The heritability estimates for AFC ranged from 0.02 +/- 0.02 to 0.04 +/- 0.02. The estimates of additive direct heritabilities (with standard error) for BW365, BW450, SC365, SC450, SC550 and SC730 were 0.36 +/- 0.07, 0.38 +/- 0.07, 0.48 +/- 0.07, 0.65 +/- 0.07, 0.64 +/- 0.07 and 0.42 +/- 0.07, respectively, and the genetic correlations with AFC were -0.38, -0.33, 0.10, -0.13, -0.13 and 0.06, respectively. In the herds studied, selection for SC365, SC450, SC550 or SC730 should not cause genetic changes in AFC. Selection based on BW365 or BW450 would favor smaller AFC breeding values. However, the low magnitude of direct heritability estimates for AFC in these farms indicates that changes in phenotypical expression depend mostly on non-genetic factors.

Evaluation of the performance of normal elderly in a limb praxis protocol: Influence of age, gender, and education

Limb praxis can be influenced by age, gender, and education. The present Study investigated the influence of these variables on gesture production by healthy elderly Subjects. We evaluated 96 individuals divided into two age groups (60-74 and 75-88 years). Each group contained 48 men and 48 women and was subdivided into four groups according to education: illiterates and 1-3, 4-7, and 8 or more years of education. Individuals were requested to carry Out tasks oil verbal command and imitation. There were no differences between the performance of men and women, while older individuals performed worse than their younger counterparts. Regarding educational level, three major groups emerged: illiterates, individuals with 1-7 years of education, and those with 8 or more years of education. In conclusion, age and education significantly influenced the performance of individuals in limb praxis tests. (JINS, 2009, 157 618-622.)

Rasmussen encephalitis: long-term outcome after surgery

Rasmussen encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis, and unilateral hemispheric atrophy. The progression of the symptoms to significant neurological impairment usually occurs within months to a few years. RE causes are unknown, although evidence of an autoimmune process has been extensively described in the literature. Antiepileptic drugs are usually not effective to control seizures or cerebral atrophy; despite data supporting a beneficial effect of early immunosuppressive and immunomodulatory interventions, for intractable seizures in RE patients with advanced disease, epilepsy surgery in the form of hemispheric disconnection has been considered the treatment of choice. This work describes the clinical and electrographic analyses, as well as the post-operative evolution of patients with RE. This work includes all the patients with RE evaluated from January 1995 to January 2008 by the RibeirA o pound Preto Epilepsy Surgery Program (CIREP), taking variables such as gender; age at epilepsy onset; seizure semiology; seizure frequency; interictal and ictal electroencephalographic (EEG) findings; age at surgery, when done; duration of epilepsy; surgery complications; follow-up duration; anatomo-pathological findings; post-surgery seizure; language and cognitive outcome; and anti-epileptic drug treatment after surgery into account. Twenty-five patients were evaluated; thirteen were female. Mean age of epilepsy onset was 4.4 +/- 2.0 years. There were no differences between patients with slow and fast evolution with respect to age of epilepsy onset (p = 0.79), age at surgery (p = 0.24), duration of epilepsy (0.06), and follow-up (p = 0.40). There were no correlations between the presence of bilateral EEG abnormalities or the absence of spikes and post-operative seizure outcome (p = 0.06). Immunomodulatory therapy was tried in 12 patients (48%). Twenty-three patients underwent surgery. The mean follow-up was 63.3 months. Eleven patients had total seizure control. Twelve individuals persisted with seizures consisting of mild facial jerks (six patients), occasional hemigeneralized tonic-clonic seizures (three patients), and frequent tonic-clonic seizures (three patients). Mental and language impairment was observed in 15 and 12 patients, after surgery, respectively. Eight patients presented post-operative cognitive decline, while only two patients had cognitive improvement. Comparing pre- and post-operative language deficits, 66.7% of the 12 patients with language disturbance did not improve after surgery. This retrospective study reported the clinical and electrographic analysis, as well as the evolution of 23 patients with RE. Patients were divided into two groups: fast evolution and slow evolution to hemiparesis and epilepsia partialis continua. These groups may represent different RE substrates. Fourteen patients achieved satisfactory seizure control, three patients had partial response to surgery, and five patients had maintenance of the pre-operative condition. All patients with left-side involvement presented with some language disturbance, which did not improve after surgery in 66.6% of patients. Cognitive evaluation showed that the majority of the patients did not have any significant improvement, and 38.1% had cognitive deterioration after surgery.

Cannabis use before age 15 and subsequent executive functioning

Background Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. Aims To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. Method We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). Results The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. Conclusions Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1)

Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process to the negative selection of autoreactive thymocytes. This phenomenon was termed ""promiscuous gene expression"" (PGE), which is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of autoimmune diseases are largely unknown, though it may be a result of a chronological effect. Although the effect of Aire mutations in pathogenic autoimmunity is well know, it could not be a unique cause for autoimmunity. Independently of mutations, temporal deregulation of Aire expression may imbalance Aire-dependent PTAs and/or wide PGE. This deregulation may be an early warning sign for autoimmune diseases as it guarantees autoantigen representation in the thymus. To assess this hypothesis, we studied the expression levels of Aire, Aire-dependent (Ins2) and Aire-independent (Gad67 and Col2a1) PTAs using real-time-PCR of the thymic stromal cells of NOD mice during the development of autoimmune type 1 diabetes mellitus (DM-1). Wide PGE was studied by microarrays in which the PTA genes were identified through parallel CD80(+) mTEC 3.10 cell line expression profiling. The results show that Aire gene was down-regulated in young pre-autoimmune (pre-diabetic) NOD mice. PGE and specific PTA genes were down-regulated in adult autoimmune diabetic animals. These findings represent evidence indicating that chronological deregulation of genes important to negative selection may be associated with the development of an autoimmune disease (DM-1) in mice.

The influence of age on blood pressure evaluation of hypertensive subjects

The aim of this study was to determine whether age influences the concordance between different methods of blood pressure (BP) measurement and ambulatory BP monitoring (ABPM) in hypertensive subjects. We studied two groups: I, individuals younger than 50 years (n = 57), and II, individuals aged 60 years or older (n = 55). They were submitted to the performance of one ABPM, office BP measurements, home BP monitoring (HBPM), and BP measurements at a public health center (PHCBP). Student`s t-test, Fisher`s test and Lin coefficient were calculated. For Group II, systolic and diastolic pressures measured by HBPM were higher than by day ABPM (p < 0.01). The concordance between day ABPM and the other methods was lower for Group II than for Group I. There was a good concordance between systolic day ABPM and office BP, and between systolic ABPM and PHCBP only for Group I (Lin coefficient = 0.71 and 0.73). Group II reported better sleep quality after ABPM (p < 0.05). Considering 24-h ABPM, 52.6% of Group I and 29% of Group II were controlled (p < 0.01). Concluding, there was worse concordance between different methods of BP measurements and day ABPM in the older group, which had lower hypertension control rate and better tolerance of ABPM. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Reliability of short comparative genomic hybridization in fibroblasts and blastomeres for a comprehensive aneuploidy screening: first clinical application

BACKGROUND: Comparative genomic hybridization (CGH) is a valuable alternative to fluorescence in situ hybridization (FISH) for preimplantation genetic screening (PGS) because it allows full karyotype analysis. However, this approach requires the cryopreservation of biopsied embryos until results are available. The aim of this study is to reduce the hybridization period of CGH, in order to make this short-CGH technique suitable for PGS of Day-3 embryos, avoiding the cryopreservation step. METHODS: Thirty-two fibroblasts from six aneuploid cell lines (Coriell) and 48 blastomeres from 10 Day-4 embryos, discarded after PGS by FISH with 9 probes (9-chr-FISH), were analysed by short-CGH. A reanalysis by the standard 72 h-CGH and FISH using telomeric probes was performed when no concordant results between short-CGH and FISH diagnosis were observed. The short-CGH was subsequently applied in a clinical case of advanced maternal age. RESULTS: In 100% of the fibroblasts analysed, the characteristic aneuploidies of each cell line were detected by short-CGH. The results of the 48 blastomeres screened by short-CGH were supported by both 72 h-CGH results and FISH reanalysis. The chromosomes most frequently involved in aneuploidy were 22 and 16, but aneuploidies for the other chromosomes, excepting 1, 10 and 13, were also detected. Forty-one of the 94 aneuploid events observed (43.6%) corresponded to chromosomes which are not analysed by 9-chr-FISH. CONCLUSIONS: We have performed a preliminary validation of the short-CGH technique, including one clinical case, suggesting this approach may be applied to Day-3 aneuploidy analysis, thereby avoiding embryo cryopreservation and perhaps helping to improve implantation rate after PGS.

A modified orthodontic protocol for advanced periodontal disease in Class II division 1 malocclusion

An interdisciplinary approach is often the best option for achieving a predictable outcome for an adult patient with complex clinical problems. This case report demonstrates the combined periodontal/orthodontic treatment for a 49-year-old woman presenting with a Class II Division 1 malocclusion with moderate maxillary anterior crowding, a 9-mm overjet, and moderate to severe bone loss as the main characteristics of the periodontal disease. The orthodontic treatment included 2 maxillary first premolar extractions through forced extrusion. Active orthodontic treatment was completed in 30 months. The treatment outcomes, including the periodontal condition, were stable 17 months after active orthodontic treatment. The advantages of this interdisciplinary approach are discussed. Periodontally compromised orthodontic patients can be satisfactorily treated, achieving most of the conventional orthodontic goals, if a combined orthodontic/periodontic approach is used. (Am J Orthod Dentofacial Orthop 2011; 139:S133-44)

Effect of growth hormone on in vitro osteogenesis and gene expression of human osteoblastic cells is donor-age-dependent

it has been demonstrated that the effect of GH on bone tissue is reduced with aging. In this study we tested the hypothesis that the action of GH on osteoblastic cells is donor-age-dependent by investigating the effect of GH on the development of osteoblastic phenotype in cultures of cells from adolescents (13-16 years old), young adults (18-35 years old), and adults (36-49 years old). Osteoblastic cells derived from human alveolar bone were cultured with or without GH for periods of up to 21 days, and parameters of in vitro osteogenesis and gene expression of osteoblastic markers were evaluated. GH increased culture growth, collagen content and alkaline phosphatase (ALP) activity in cultures from adolescents and young adults, whereas non-significant effect was observed in cultures from adults. While GH significantly increased the bone-like formation in cultures from adolescents, a slightly effect was observed in cultures from young adults and no alteration was detected in cultures from adults. Results from real-time PCR demonstrated that GH upregulated ALP, osteocalcin, type I collagen, and Cbfa1 mRNA levels in cultures from adolescents. In addition, cultures from young adults showed higher ALP mRNA expression and the expression of all evaluated genes was not affected by GH in cultures from adults. These results indicate that the GH effect on both in vitro osteogenesis and gene expression of osteoblastic markers is donor-age-dependent, being more pronounced on cultures from adolescents.