The genetic structure of 3 ` untranslated region of the HLA-G gene: polymorphisms and haplotypes

The HLA-G gene is predominantly expressed at the maternal-fetal interface. It has been associated with maternal-fetal tolerance and in the inhibition of cytotoxic T lymphocyte and natural killer cytolytic functions. At least two variations in the 3` untranslated region (UTR) of HLA-G locus are associated with HLA-G expression levels, the 14-bp deletion/insertion polymorphism and the +3142 single-nucleotide polymorphism (SNP). However, this region has not been completely characterized yet. The variability of the 3`UTR of HLA-G gene and its haplotype structure were characterized in 155 individuals from Brazil, as well as HLA-G alleles associated with each of the 3`UTR haplotype. The following eight variation sites were detected: the 14-bp polymorphism and SNPs at the positions +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and +3196C/G. Similarly, 11 different 3`UTR haplotypes were identified and several HLA-G alleles presented only one 3`UTR haplotype. In addition, a high linkage disequilibrium among the variation sites was detected, especially among the 14-bp insertion and the alleles +3142G and +3187A, all previously associated with low mRNA availability, demonstrating that their effects are not independent. The detailed analyses of 3`UTR of the HLA-G locus may shed some light into mechanisms underlying the regulation of HLA-G expression. Genes and Immunity (2010) 11, 134-141; doi: 10.1038/gene.2009.74; published online 1 October 2009

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.)

Long-Term Ethanol Consumption Promotes Hepatic Tumorigenesis but Impairs Normal Hepatocyte Proliferation in Rats

Chronic and excessive alcohol consumption has been related to an increased risk of several cancers, including that of the liver; however, studies in animal models have yet to conclusively determine whether ethanol acts as a tumor promoter in hepatic tumorigenesis. We examined whether prolonged alcohol consumption could act as a hepatic tumor promoter after initiation by diethylnitrosamine (DEN) in a rat model. Male Sprague-Dawley rats were injected with 20 mg DEN/kg body weight 1 wk before introduction of either an ethanol liquid diet or an isoenergic control liquid diet. Hepatic pathological lesions, hepatocyte proliferation, apoptosis, PPAR alpha and PPAR gamma, and plasma insulin-like growth factor 1 IGF-1) levels were assessed after 6 and 10 mo. Mean body and liver weights, plasma IGF-1 concentration, hepatic expressions of proliferating cellular nuclear antigen and Ki-67, and cyclin D1 in ethanol-fed rats were all significantly lower after 10 mo of treatment compared with control rats. In addition, levels of hepatic PPAR gamma protein, not PPAR alpha, were significantly higher in the ethanol-fed rats after prolonged treatment. Although ethanol feeding also resulted in significantly fewer altered hepatic foci, hepatocellular adenoma was detected in ethanol-fed rats at 10 mo, but not in control rats given the same dose of DEN. Together, these results indicate that chronic, excessive ethanol consumption impairs normal hepatocyte proliferation, which is associated with reduced IGF-1 levels, but promotes hepatic carcinogenesis. J. Nutr. 141: 1049-1055, 2011.

Influence of aging, tidal volume, and respiratory rate on Doppler echocardiographic indices of diastolic function in normal male subjects: A quantitative evaluation

Background: Although the influence of respiration on ventricular filling, as evaluated by Doppler technique, and the evaluation of diastolic velocities of mitral valve annulus (MVA), as measured by Doppler tissue imaging (DTI), can provide valuable information for the study of left ventricular (LV) diastolic function, the concomitant effects of aging, tidal volume (TV), and respiratory rate (RR) on these velocities have not been quantitatively investigated. Methods: We evaluated 12 normal male volunteers (Group I) aged 20-26 years (mean: 22.8) and 8 normal subjects aged 41 to 54 years old (mean: 45.9) (Group II). Using DTI we measured peak early (E-a) and late (A(a)) velocities of longitudinal axis expansion at lateral and medial MVA. Doppler mitral and tricuspid flow velocities were measured: peak early (E) and late (A) inflow velocity, early (E-i) and late (A(i)) flow integral, and deceleration time of peak early mitral flow velocity (DT). Respiratory cycles were simultaneously recorded at RR of 9, 12, 15, and 18 cycles/min and TV of 600 and 900 mL during respiration (RESP). Results and conclusions: (1) E, A, and A(i) in MV had negligible change during respiration, but E-i was significantly reduced during inspiration; (2) DT reduced slightly with inspiration, but the change was significant only with TV of 900 mL; (3) an important increase of E in right ventricular flow was observed during inspiration; (4) variations of RR and TV did not significantly influence right and left ventricular inflow in normal subjects, in the conditions of this investigation; (5) a significant increase of E-a at medial MVA was documented during inspiration only in young subjects; (6) a significant decrease of A(a) at medial MVA was observed during inspiration in both groups of volunteers; (7) RR and TV did not influence MVA velocities in young and adult subjects; (8) a consistent reduction in E-a and a significant increase in A(a) were observed with increasing age; (9) these changes were more conspicuous and consistent than those documented in ventricular filling when young and middle-age men are compared, suggesting that the DTI is more sensitive to detect changes in diastolic function; and (10) in addition, these data suggest that, for evaluation of diastolic function, in clinical context, it is not necessary to control rigorously RR or TV.

Articular Cartilage in the Knee: Current MR Imaging Techniques and Applications in Clinical Practice and Research

Magnetic resonance (MR) imaging is the most important imaging modality for the evaluation of traumatic or degenerative cartilaginous lesions in the knee. It is a powerful noninvasive tool for detecting such lesions and monitoring the effects of pharmacologic and surgical therapy. The specific MR imaging techniques used for these purposes can be divided into two broad categories according to their usefulness for morphologic or compositional evaluation. To assess the structure of knee cartilage, standard spin-echo (SE) and gradient-recalled echo (GRE) sequences, fast SE sequences, and three-dimensional SE and GRE sequences are available. These techniques allow the detection of morphologic defects in the articular cartilage of the knee and are commonly used in research for semiquantitative and quantitative assessments of cartilage. To evaluate the collagen network and proteoglycan content in the knee cartilage matrix, compositional assessment techniques such as T2 mapping, delayed gadolinium-enhanced MR imaging of cartilage (or dGEMRIC), T1 rho imaging, sodium imaging, and diffusion-weighted imaging are available. These techniques may be used in various combinations and at various magnetic field strengths in clinical and research settings to improve the characterization of changes in cartilage. (C)RSNA, 2011 , radiographics.rsna.org

Grade II atypical choroid plexus papilloma with normal karyotype

Cytogenetic studies of atypical choroid plexus papillomas (CPP) have been poorly described. In the present report, the cytogenetic investigation of an atypical CPP occurring in an infant is detailed. CPP chromosome preparations were analyzed by giemsa-trypsin-banding (GTG-banding) and comparative genome hybridization (CGH). Conventional karyotype analysis of tumor culture showed a normal chromosome complement. The results were confirmed by CGH, showing normal hybridization patterns for the sample. To date, the few atypical CPPs described in the literature have shown disparate cytogenetic information. This is the first report of a normal chromosome complement in atypical CPP. The heterogenic genetic features observed in these small series may reflect the diverse genetic background of choroid plexus tumors in children.

Effects of Nicotine Exposure on Renal Function of Normal and Hypercholesterolemic Rats

Background/Aims: Renal risks of nicotine exposure associated with hypercholesterolemia are still unknown. Methods: Thus, hypercholesterolemic rats (HC) and their control (C) were evaluated by inulin clearance (InCl) measured at baseline and during nicotine infusion (100 mu g/kg b.w.). Five groups were studied: (i) C; (ii) DEN (C submitted to a renal denervation); (iii) C + L-arginine (0.25% in drinking water); (iv) HC, and (v) HC + L-arginine (0.25% in drinking water). Furthermore, C and HC had their renal blood flow (RBF) measured and they have also been chronically treated with nicotine (12.5 mu g/ml in drinking water) to assess InCl on the 8th day. Results: Nicotine increased blood pressure in C, DEN and HC and reduced InCl only in C. L-Arginine treatment blunted nicotine effects on blood pressure and increased InCl only in C. Moreover, nicotine did not change RBF in C but elicited in HC, whereas renal vascular resistance was increased in C and unchanged in HC. Indeed, chronic nicotine exposure has also reduced InCl in C. Conclusion: Nicotine acted on the adrenergic system and nitric oxide counteracted this action in C, but the same may not be applied to HC. An impairment in renal autoregulation may explain why InCl was unchanged in HC. Copyright (C) 2009 S. Karger AG, Basel

Focal and linear endocardial and epicardial catheter-based cryoablation of normal and infarcted ventricular tissue

Background: This study of a chronic porcine postinfarction model examined whether linear epicardial cryoablation was capable of creating large, homogenous lesions in regions of the myocardium including scarred ventricle. Endocardial and epicardial focal cryolesions were also compared to determine if there were significant differences in lesion characteristics. Methods: Eighty focal endocardial and 28 focal epicardial cryoapplications were delivered to eight normal caprine and four normal porcine ventricular myocardium, and 21 linear cryolesions were applied along the border of infarcted epicardial tissue in a chronic porcine infarct model in six swines. Results: Focal endocardial cryolesions in normal animals measured 9.7 +/- 0.4 mm (length) by 7.3 +/- 1.4 mm (width) by 4.8 +/- 0.2 mm (depth), while epicardial lesions measured 10.2 +/- 1.4 mm (length) by 7.7 +/- 2 mm (width) by 4.6 +/- 0.9 mm (depth); P > 0.05. Linear epicardial cryolesions in the chronic porcine infarct model measured 36.5 +/- 7.8 mm (length) by 8.2 +/- 1.3 mm (width) by 6.0 +/- 1.2 mm (depth). The mean depth of linear cryolesions applied to the border of the infarct scar was 7 +/- 0.7 mm, as measured by magnetic resonance imaging. Conclusions:Cryoablation can create deep lesions when delivered to the ventricular epicardium. Endocardial and epicardial cryolesions created by a focal cryoablation catheter are similar in size and depth. The ability to rapidly create deep linear cryolesions may prove to be beneficial in substrate-based catheter ablation of ventricular arrhythmias.

Population structure and mouse-virulence of Toxoplasma gondii in Brazil

Recent studies found that isolates of Toxoplasma gondii from Brazil were biologically and genetically different from those in North America and Europe. However, to date only a small number of isolates have been analysed from different animal hosts in Brazil. In the present study DNA samples of 46 T. gondii isolates from cats in 11 counties in Sao Paulo state, Brazil were genetically characterised using 10 PCR restriction fragment length polymorphism markers including SAG1, SAG2, SAG3, STUB, GRA6, c22-8, c29-2, L358, PKI and Apico. An additional marker, CS3, that locates on chromosome VIIa and has previously been shown to be linked to acute virulence of T. gondii was also used to determine its association to virulence in mice. Genotyping of these 46 isolates revealed a high genetic diversity with 20 genotypes but no clonal Type I, II or III lineage was found. Two of the 46 isolates showed mixed infections. Combining genotyping data in this study with recent reported results from chickens, dogs and cats in Brazil (total 125 isolates) identified 48 genotypes and 26 of these genotypes had single isolates. Four of the 48 genotypes with multiple isolates identified from different hosts and locations are considered the common clonal lineages in Brazil. These lineages are designated as Types BrI, BrII, BrIII and BrIV. These results indicate that the T. gondii population in Brazil is highly diverse with a few successful clonal lineages expanded into wide geographical areas. In contrast to North America and Europe, where the Type II clonal lineage is overwhelmingly predominant, no Type II strain was identified from the 125 Brazil isolates. Analysis of mortality rates in infected mice indicates that Type BrI is highly virulent, Type BrIII is non-virulent, whilst Type BrII and BrIV lineages are intermediately virulent. In addition, allele types at the CS3 locus are strongly linked to mouse-virulence of the parasite. Thus, T. gondii has an epidemic population structure in Brazil and the major lineages have different biological traits. (C) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Cell cycle and apoptosis in normal and cloned bovine near-term placentae

The bovine maternal epithelium is composed of cuboidal cells interspersed with low columnar cells having centrally located nuclei. Bovine trophoblast is composed of two cell types: mononuclear trophoblastic and giant trophoblastic cells that can have two or more nuclei. Number of apoptotic cells and proliferative cells are variable in both cell populations. This study compared tissue growth and apoptosis by flow cytometry in the cell population found at distinct placental regions (central region of placentomes, <= 1-cm microplacentomes and the interplacentomal region) between normal and cloned near-term bovine pregnancies. After a morphological comparison between regions and groups (controls vs. clones), a lesser proportion of diploid to tetraploid cells was observed in the central region of placentomes and in microplacentomes from cloned-derived pregnancies. In addition, cloned animals had a fewer apoptotic cells in the central region of the placentome and in interplacentomal region and a greater proliferative capacity in all regions (cells in G(2)/M) near term as opposed to control animals. These results may reveal the existence of a relationship between such changes in the proportions of uterine and trophoblastic epithelial cells at the end of pregnancy and normal placental function. This could be related to faulty placentation in early pregnancy, placental insufficiency during pregnancy or lack of placental and/or fetal maturation in late pregnancy, which may contribute to someof the abnormalities after in vitro embryo manipulations, such as poor preparation and initiation of parturition, prolonged gestation and lesser post-natal survival in some cloned animals. (C) 2008 Elsevier B.V. All rights reserved.

Peripartum Haemodynamic Status of Bitches with Normal Birth or Dystocia

There has been limited investigation of parturition in the bitch and there is little information published on clinical and obstetrical examination other than opinion and anecdote. While there are substantial data on haemodynamic and vascular changes during normal parturition in humans, little is known about the physiological events in the dog. This study was aimed at maternal haemodynamic changes occurring during normal parturition and to investigate how these were modified in bitches with dystocia (DYST) treated either medically or via assisted delivery and caesarean operation. Three groups of 10 bitches were investigated; those with normal parturition, those with DYST corrected by manipulative assistance or caesarean operation and those with uterine inertia treated by oxytocin administration. Heart rate, systolic and diastolic blood pressure, electrocardiogram and blood glucose concentration were measured pre-partum, intra-partum, immediately after parturition and 1 h later. Heart rate was high at all times throughout the study and the majority of bitches had normal sinus rhythm. Blood pressure was generally within the normal range, and although systolic and diastolic blood pressure was highest during the intra-partum period and sometimes during the immediate post-partum period, there were no significant differences between groups. All bitches had blood glucose concentrations within the normal range throughout the study although pre-partum concentrations were statistically lower than many of the other time periods. The study provides useful physiological data that will facilitate monitoring and clinical management of bitches throughout normal parturition and DYST.

Neonatal Clinical Evaluation, Blood Gas and Radiographic Assessment After Normal Birth, Vaginal Dystocia or Caesarean Section in Dogs

This study aimed to standardize signs and diagnostic criteria of respiratory function in newborn puppies delivered normally or after dystocia and caesarean operation. A total of 48 neonates were allocated into groups: eutocia (n = 20), dystocia (n = 8), caesarean (c)-section (n = 20). Neonatal health was assessed using the Apgar score and body temperature was determined at 0, 5 and 60 min after delivery. Venous blood gases (pO(2) and SO(2)) was measured immediately and 60 min after delivery, and a thoracic radiograph was made between 0 and 5 min of life. The c-section group had significantly lower Apgar scores at birth and 5 min. Hypothermia was present at 5 min in the eutocia and c-section groups, and at 60 min in all groups. The eutocia group had an irregular respiratory pattern in 78% of puppies at birth, 27.7% at 5 min and 21% at 60 min compared with 87.5%, 62.5% and 12.5% of the pups in the dystocia group where there was irregular respiratory rhythm, moderate to intense respiratory sounds with agonic episodes. The c-section group had respiratory alterations in 70%, 45% and 16% of puppies at 0, 5 and 60 min, respectively. Radiographic abnormalities were present in 17% of the pups in the eutocia group, 25% of the pups in the dystocia group and 30% of the pups in the c-section group, respectively. The c-section group had significantly lower SO(2) values at 60 min than at birth. All puppies had hypoxaemia, but a significant decrease was observed in the c-section group. Newborn puppies had tissue hypoxia and irregular respiratory pattern at birth. Caesarean-section puppies had lower vitality; however, all developed satisfactory Apgar scores at 5 min of life, regardless of the obstetric condition.