Gender-Specific Differences in Fetal Cardiac Troponin T in Pregnancies Complicated by Placental Insufficiency

Background: Placental insufficiency and fetal growth restriction may lead to fetal hypoxia and acidemia, which result in fetal cardiac injury. Objective: The goal of this study was to compare the levels of fetal cardiac troponin T (cTnT) at birth and fetal Doppler parameters according to fetal gender in pregnancies complicated by placental insufficiency before 34 weeks` gestation. Methods: Between March 2007 and November 2010, singleton pregnancies with placental insufficiency characterized by abnormal umbilical artery Doppler results were prospectively studied. All the patients delivered by cesarean section, and Doppler examinations were performed up to 48 hours before birth. Immediately after delivery, umbilical artery blood samples were obtained for fetal cTnT measurements. Results: Fifty high-risk pregnant women met the study criteria. The study groups were as follows: group 1 consisted of 23 male fetuses (46%) and group 2 consisted of 27 female fetuses (54%). cTnT levels were significantly higher in the group of male fetuses (median, 0.14; range, 0.01-0.85) compared with the group of female fetuses (median, 0.05; range, 0.01-0.27) (P = 0.039). In the group of male fetuses, Doppler results of the ductus venosus assessment revealed values of pulsatility index for veins >= 1.0 in 15 male fetuses (65.2%) and 9 female fetuses (33.3%) (P = 0.032). Conclusions: Fetal gender was associated with cTnT level at birth in pregnancies complicated by placental insufficiency before 34 weeks` gestation, although the Doppler findings did not support gender differences. The fetal cardiac compromise and cardiac injury may be influenced by fetal gender, suggesting differences in the cardiovascular response to fetal hypoxia. (Gend Med. 2011;8:202-208) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.

Seroprevalence of Human Papillomavirus 6, 11, 16, and 18 in Young Primiparous Women in Sao Paulo, Brazil

Introduction: Data on epidemiology of HPV infection are needed for the development of human papillomavirus (HPV) vaccine recommendations, especially in countries where HPV vaccination is not yet included in public vaccination programs. The aim of this study was to determine the prevalence of serum antibodies to HPV types 6, 11, 16, and 18 and associated factors among young women after birth of the first child. Methods: This cross-sectional study was carried out in a large public maternity hospital in Sao Paulo, Brazil. Three hundred one women aged 15 to 24 years who gave birth to their first child were recruited between 43 and 60 days after delivery. Seroprevalence was performed using a type-specific enzyme-linked immunosorbent assay based on HPV Late protein 1 viruslike particles. The association of seroreactivity with these 4 HPV types with selected demographic and behavioral factors was assessed by Generalized Linear Model analysis. Results: Fifty-eight (19.3%) women (95% confidence interval, 15.0%-24.2%) had antibodies to any of the 4 viruslike particles tested. The overall seroprevalence rates of the HPV types were: HPV16, 9.0%; HPV18, 7.0%; and HPV 6+11, 7.7%, which are targeted by the HPV prophylactic vaccines. In the multivariate analysis, only age (inversely, P = 0.044 for trend) and previous sexually transmitted disease (P = 0.008) were 2 factors independently associated with HPV seropositivity. Conclusions: These data offer additional information on the epidemiology of HPV in a group of young Brazilian women after first delivery and contribute to establish a baseline of HPV seroprevalence against which post-HPV vaccine era seroprevalence can be compared.

Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions

Background Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Methods Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). Results HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). Conclusions A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 x 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 x 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658-64. (C) 2011 AACR.

Profile of Autoantibodies Against Phosphorylcholine and Cross-reactivity to Oxidation-Specific Neoantigens in Selective IgA Deficiency With or Without Autoimmune Diseases

Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

Preterm and term neonates transplacentally acquire IgG antibodies specific to LPS from Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa

High incidences of Gram-negative bacteria are found in neonatal nosocomial infections. Our aim was to investigate placental transmission of immunoglobulin G (IgG) reactive with lipopolysaccharide from Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia colt O111, O6 and O26. The total and lipopolysaccharide-specific IgM and IgG were determined in 11 maternal/umbilical-cord sera aged <= 33 weeks (GI); 21 aged > 33 and < 37 weeks (GII); and 32 term newborns (GIII). The total and lipopolysaccharide-specific IgM concentrations were equivalent in maternal sera. The total IgG concentrations were equivalent in maternal and newborn sera, with the exception of GIII newborns as compared with their mothers (P < 0.0001) and with neonates from GI and GII (P < 0.05). Lipopolysaccharide-specific IgG concentrations were lower in GI neonates than in their mothers (P < 0.01) and lower in GII (P < 0.05). Lower lipopolysaccharide-specific IgG levels were observed among neonates only for O111 in GI (P < 0.05) and for 026 and Pseudomonas in GII, both as compared with GIII (P < 0.05). The anti-lipopolysaccharide IgG transfer ratios were lower in GI (except for 026) and in GII (except for Klebsiella and O111) as compared with GIII (P < 0.05). Our results suggest that the greater susceptibility to infections in preterm infants is influenced (besides the humoral response) by factors intrinsic and extrinsic to the condition of prematurity.

Development of Y-chromosome-Specific SCAR Markers Conserved in Taurine, Zebu and Bubaline Cattle

Contents Sex pre-selection of bovine offsprings has commercial relevance for cattle breeders and several methods have been used for embryo sex determination. Polymerase chain reaction (PCR) has proven to be a reliable procedure for accomplishing embryo sexing. To date, most of the PCR-specific primers are derived from the few single-copy Y-chromosome-specific gene sequences already identified in bovines. Their detection demands higher amounts of embryonic genomic material or a nested amplification reaction. In order to circumvent this, limitation we searched for new male-specific sequences potentially useful in embryo sexing using random amplified polymorphic DNA (RAPD) analysis. Random amplified polymorphic DNA (RAPD) assay reproducibility problems can be overcome by its conversion into Sequence Characterized Amplified Region (SCAR) markers. In this work, we describe the identification of two bovine male-specific markers (OPC16(323) and OPF10(1168)) by means of RAPD. These markers were successfully converted into SCARs (OPC16(726) and OPF10(984)) using two pairs of specific primers.Furthermore, inverse PCR (iPCR) methodology was successfully applied to elongate OPC16(323) marker in 159% (from 323 to 837 bp). Both markers are shown to be highly conserved (similarity >= 95%) among bovine zebu and taurine cattle; OPC16(323) is also highly similar to a bubaline Y-chromosome-specific sequence. The primers derived from the two Y-chromosome-specific conserved sequences described in this article showed 100% accuracy when used for identifying male and female bovine genomic DNA, thereby proving their potential usefulness for bovine embryo sexing.

Arterial and interstitial remodelling processes in non-specific interstitial pneumonia: systemic sclerosis versus idiopathic

Aims: To compare septal and vascular matrix remodelling, vascular occlusion, Pulmonary function tests and survival between two groups: one with idiopathic non-specific interstitial pneumonia (NSIP) and one with NSIP associated with systemic sclerosis (SSc). Methods and results: Pulmonary biopsy specimens were examined from 40 patients, 22 with NSIP and 18 with NSIP associated with SSc. The content of septal collagen and elastic fibres, as well as the elastic fibres in the vascular interstitium, were higher in the SSc group (P = 0.01, P = 0.001 and P < 0.0001, respectively). Among pulmonary function tests. the diffusing capacity for carbon monoxide/alveolar volume was affected to a greater extent in the SSc group (59%) of the predicted value in SSc and 97% in the idiopathic group). There were no differences in collagen content of the vascular interstitium, arterial occlusion, or survival between the two groups. Conclusions: Although the fibrotic process is more intense in the SSc group. it, does not affect the prognosis of these patients. Because the elastotic process is higher in the SSc group, this might suggest that autoimmune inflammatory mechanisms affecting the elastic fibre system play a greater role in the pathogenesis and pulmonary remodelling process of SSc NSIP than in idiopathic NSIP.

Leishmania chagasi infection in cats with dermatologic lesions from an endemic area of visceral leishmaniosis in Brazil

Although dogs are considered the main domestic reservoirs for Visceral Leishmaniosis (VL), which is caused in the Americas by Leishmania chagasi, infected cats have also been recently found in endemic areas of several countries and became a public health concern. Accordingly, the purpose of this study was to evaluate cats with dermatologic lesions from an endemic area of VL and the natural infection of L. chagasi. A total of 55 cats were selected between April 2008 and November 2009 from two major animal shelters of Aracatuba, Southeastern Brazil. All cats underwent general and dermatologic examinations, followed by direct parasitological examination of lymphoid organs, immunosorbent assay (ELISA) and indirect immunofluorescence (IFAT). In addition, detection of amastigotes was performed by immunohistochemistry (IHC) in skin lesions of all cats. VL was diagnosed in 27/55 (49.1%) cats with dermatological problems. Amastigotes were found in lymphoid organs of 10/27 (37.0%) cats; serology of 14/27 (51.9%), 6/27 (22.2%) and 5/27 (18.5%) cats was positive for ELISA, IFAT and both, respectively. The IHC identified 9/27 (33.3%) cats; 5/27 (18.5%) were positive only for IHC and therefore increased the overall sensitivity. Specific FIV antibodies were found in 6/55(10.9%) cats, of which 5/6 (83.3%) had leishmaniosis. Real time PCR followed by amplicon sequencing successfully confirmed L chagasi infection. In conclusion, dermatological lesions in cats from endemic areas was highly associated to visceral leishmaniosis, and therefore skin IHC and differential diagnosis of LV should be always conducted in dermatological patients in such areas. (c) 2011 Elsevier B.V. All rights reserved.

COMBINATION OFGENERAL AND SPECIFICWARM-UPS IMPROVES LEG-PRESS ONE REPETITION MAXIMUM COMPARED WITH SPECIFIC WARM-UP IN TRAINED INDIVIDUALS

Abad, CCC, Prado, ML, Ugrinowitsch, C, Tricoli, V, and Barroso, R. Combination of general and specific warm-ups improves leg-press one repetition maximum compared with specific warm-up in trained individuals. J Strength Cond Res 25(8): 2242-2245, 2011-Accurate assessment of muscular strength is critical for exercise prescription and functional evaluation. The warm-up protocol may affect the precision of the 1 repetition maximum (1RM) test. Testing guidelines recommend performing both general and specific warm-ups before strength tests. The general warm-up intends to raise muscle temperature, whereas the specific warm-up aims to increase neuromuscular activation. Although there is scientific evidence for performing the specific warm-up, the effects of general warm-up on strength tests are still unclear. The purpose of this study was to investigate whether the combination of a general with a specific warm-up (G + SWU) protocol would improve leg press 1RM values compared with a specific warm-up (SWU) protocol. Thirteen participants were tested for leg-press 1RM under 2 warm-up conditions. In the first condition, participants performed the SWU only, which was composed of 1 set of 8 repetitions at approximately 50% of the estimated 1RM followed by another set of 3 repetitions at 70% of the estimated 1RM. In the second condition (G + SWU), participants performed the 1RM test after a 20-minute general warm-up on a stationary bicycle at 60% of HRmax and the same specific warm-up as in the SWU. Values of 1RM in SWU and in G + SWU were compared by a paired t-test, and significance level was set at p <= 0.05. Strength values were on average 8.4% (p = 0.002) higher in the G + SWU compared with the SWU. These results suggest that the G + SWU induced temperature-dependent neuromuscular adjustments that increased muscle force production capacity. Therefore, these results support the recommendations of the testing guidelines to perform a moderate intensity general warm-up in addition to the specific warm-up before maximum strength assessments.

Evaluation of RET polymorphisms in a six-generation family with G533C RET mutation: specific RET variants may modulate age at onset and clinical presentation

P>Context We previously described a six-generation family with G533C RET mutation and medullary thyroid carcinoma, in the largest family reported do date. Of particular interest, phenotype variability regarding the age of onset and clinical presentation of the disease, was observed. Objective We evaluate whether single SNPs within RET oncogene or haplotype comprising the RET variants (defined by Haploview) could predispose to early development of MTC in this family and influence the clinical manifestation. Design Eight SNPs were selected based on their previous association with the clinical course of hereditary or sporadic MTC, in particular promoting an early onset of disease. The variants were initially tested in 77 G533C-carriers and 100 controls using either PCR-direct sequencing or PCR-RFLP. Association between a SNP or haplotype and age at diagnosis or presence of lymph node metastasis was tested in 34 G533C-carries with MTC. Different bioinformatic tools were used to evaluate the potential effects on RNA splicing. Results An association was found between IVS1-126G > T and age at diagnosis. The variant [IVS8 +82A > G; 85-86 insC] was associated with the presence of lymph node metastases at diagnosis. In silico analysis suggested that this variant may induce abnormal splicing. This in silico analysis predicted that the [IVS8 +82A > G; 85-86 insC] could alter the splicing by disrupting and/or creating exonic splicing enhancer motifs. Conclusions We here identified two RET variants that were associated with phenotype variability in G533C-carriers, which highlights the fact that the modifier effect of a variant might depend on the type of mutation.

A Duplex Allele-Specific Amplification PCR to Detect SMN1 Deletion

Spinal muscular atrophy (SMA), the leading genetic cause of death in childhood, is an autosomal recessive neuromuscular disorder characterized by progressive muscle weakness, associated with deletions of the survival motor neuron (SMN) gene identified and mapped to chromosome 5q13. SMN is present in two highly homologous copies (SMN1 and SMN2). In the general population, normal individuals (noncarriers) have at least one telomeric (SMN1) copy, and 5% of them have no copies of SMN2. Approximately 95% of SMA patients carry homologous deletions of SMN1 exon(s) 7 (and 8). SMN1 and SMN2 exons 7 and 8 differ only by 1 bp each, and SMA diagnosis might be performed by single-strand conformational polymorphism, PCR amplification followed by restriction fragment length polymorphism (RFLP), multiple ligation-dependent probe amplification, or realtime PCR of SMNs exons 7 and 8. We developed a simpler and cost-effective method to detect SMN1 exon 7 deletion based on allele-specific amplification PCR.

Cdx2, cytokeratin 20, thyroid transcription factor 1, and prostate-specific antigen expression in unusual subtypes of prostate cancer

There are some unusual histologic variants of prostate carcinoma, including mucinous, signet-ring cells, and ductal carcinomas that can metastasize in a problematic way and simulate lung, colorectal, or bladder primaries. Currently, antibodies that are organ-specific have been used in the routine surgical pathology practice. Our aim is to study the profile of expression of Cdx2, thyroid transcription factor 1 (TTF1), and cytokeratin 20 (CK20) in prostate cancer with unusual histologic finding. Twenty-nine prostate adenocarcinomas with unusual histologic findings were submitted to immunohistochemistry with prostate-specific antigen (PSA), CK20, Cdx2, and TTF1 antibodies. There were 7 mucinous, 5 ductal, 2 signet-ring cells, and 15 usual acinar adenocarcinomas with focal mucinous differentiation. To compare the results with usual acinar adenocarcinomas, we studied 10 primary and their respective lymph node metastases in a tissue microarray, 2 unusual metastatic adenocarcinomas, and 6 usual acinar high-grade carcinomas. For tumors with special histologic finding, Cdx2 was expressed by 9 (31.0%) mucinous, signet-cell, or with focal mucinous differentiation. Thyroid transcription factor I was moderately positive in mucinous differentiation areas of 2 (6.9%) adenocarcinomas. Cytokeratin 20 was expressed by 9 (31.0%) tumors, among them, 3 ductal adenocarcinomas. Prostate-specific antigen was positive in 28 (96.6%) cases and negative in I ductal adenocarcinoma. There was only I worrisome ductal adenocarcinoma that was strongly CK20 positive and PSA negative. Almost one third of mucinous prostate carcinomas express Cdx2. Cytokeratin 20 can be positive also in one third of prostate carcinomas, especially the ductal type. Pathologist should be alert when evaluating immumohistochemical profiles of unusual histologic findings of prostate cancer, mostly in distant sites. (C) 2008 Elsevier Inc. All rights reserved.

Application of recombinant antibody library for screening specific antigens in a bovine sperm cell subpopulation

Antibody phage display libraries are a useful tool in proteomic analyses. This study evaluated an antibody recombinant library for identification of sex-specific proteins on the sperm cell surface. The Griffin.1 library was used to produce phage antibodies capable of recognizing membrane proteins from Nelore sperm cells. After producing soluble monoclonal scFv, clones were screened on Simental sperm cells by flow cytometry and those that bound to 40-60% of cells were selected. These clones were re-analyzed using Nelore sperm cells and all clones bound to 40-60% of cells. Positive clones were submitted to a binding assay against male and female bovine leukocytes by flow cytometry and one clone preferentially bound to male cells. The results indicate that phage display antibodies are an alternative method for identification of molecules markers on sperm cells. (C) 2007 Elsevier B.V. All rights reserved.

Representational Difference Analysis (RDA) reveals differential expression of conserved as well as novel genes during caste-specific development of the honey bee (Apis mellifera L.) ovary

In highly eusocial insects, such as the honey bee, Apis mellifera, the reproductive bias has become embedded in morphological caste differences. These are most expressively denoted in ovary size, with adult queens having large ovaries consisting of 150-200 ovarioles each, while workers typically have only 1-20 ovarioles per ovary. This morphological differentiation is a result of hormonal signals triggered by the diet change in the third larval instar, which eventually generate caste-specific gene expression patterns. To reveal these we produced differential gene expression libraries by Representational Difference Analysis (RDA) for queen and worker ovaries in a developmental stage when cell death is a prominent feature in the ovarioles of workers, whereas all ovarioles are maintained and extend in length in queens. In the queen library, 48% of the gene set represented homologs of known Drosophila genes, whereas in the worker ovary, the largest set (59%) were ESTs evidencing novel genes, not even computationally predicted in the honey bee genome. Differential expression was confirmed by quantitative RT-PCR for a selected gene set, denoting major differences for two queen and two worker library genes. These included two unpredicted genes located in chromosome 11 (Group11.35 and Group11.31, respectively) possibly representing long non-coding RNAs. Being candidates as modulators of ovary development, their expression and functional analysis should be a focal point for future studies. (C) 2011 Elsevier Ltd. All rights reserved.