Body Perception and Satisfaction in Obese,Severely Obese,and Normal Weight Female Patients

The objective of this study was to investigate body perception and the associated level of dissatisfaction among obese patients. Twenty patients from each category of obese, severely obese, and normal weight individuals had their pictures enlarged or thinned using a computer program to manipulate photographs taken from the front, profile angle, and back. The pictures were shown to patients to represent both the way they thought they appeared and the way they would like to appear. Our results show that severely obese patients correctly perceived themselves as being more corpulent than obese patients, who in turn correctly perceived themselves as being more corpulent than normal weight females. These results remained stable regardless of whether the pictures were taken from the front, profile angle, or back. These results are discussed in terms of clinical and therapeutic interventions.     

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression,but little interleukin-22 and interleukin-23R expression

Introduction  

Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity.     

Transition of healthy to diseased synovial tissue in rheumatoid arthritis is associated with gain of mesenchymal/fibrotic characteristics

The healthy synovial lining layer consists of a single cell layer that regulates the transport between the joint cavity and the surrounding tissue. It has been suggested that abnormalities such as somatic mutations in the p53 tumor-suppressor gene contribute to synovial hyperplasia and invasion in rheumatoid arthritis (RA). In this study, expression of epithelial markers on healthy and diseased synovial lining tissue was examined. In addition, we investigated whether a regulated process, resembling epithelial to mesenchymal transition (EMT)/fibrosis, could be responsible for the altered phenotype of the synovial lining layer in RA. Synovial tissue from healthy subjects and RA patients was obtained during arthroscopy. To detect signs of EMT, expression of E-cadherin (epithelial marker), collagen type IV (indicator of the presence of a basement membrane) and alpha-smooth muscle actin (alpha-sma; a myofibroblast marker) was investigated on frozen tissue sections using immunohistochemistry. Fibroblast-like synoviocytes (FLSs) from healthy subjects were isolated and subjected to stimulation with synovial fluid (SF) from two RA patients and to transforming growth factor (TGF)-beta. To detect whether EMT/fibrotic markers were increased, expression of collagen type I, alpha-sma and telopeptide lysylhydroxylase (TLH) was measured by real time PCR. Expression of E-cadherin and collagen type IV was found in healthy and arthritic synovial tissue. Expression of alpha-sma was only found in the synovial lining layer of RA patients. Stimulation of healthy FLSs with SF resulted in an upregulation of alpha-sma and TLH mRNA. Collagen type I and TLH mRNA were upregulated after stimulation with TGF-beta. Addition of bone morphogenetic protein (BMP)-7 to healthy FLS stimulated with SF inhibited the expression of alpha-sma mRNA. The finding that E-cadherin and collagen type IV are expressed in the lining layer of healthy and arthritic synovium indicates that these lining cells display an epithelial-like phenotype. In addition, the presence of alpha-sma in the synovial lining layer of RA patients and induction of fibrotic markers in healthy FLSs by SF from RA patients indicate that a regulated process comparable to EMT might cause the alteration in phenotype of RA FLSs. Therefore, BMP-7 may represent a promising agent to counteract the transition imposed on synoviocytes in the RA joint.     

The endoplasmic reticulum is a key component of the plasma cell death pathway

Plasma cells (PC) are the effector cells of the humoral Ab response. Unlike other dedicated secretory cells, they exist as two populations with opposite cell fates: short-lived and long-lived PC. Upon transformation they lead to an incurable neoplasia called multiple myeloma. In this study we have explored the molecular mechanism of PC death. Our data show that their apoptotic pathway is unique among other hemopoietic cells inasmuch as neither the death receptors nor the mitochondria play the central role. PC apoptosis is initiated by activation of Bax at the endoplasmic reticulum membrane and subsequent activation of the endoplasmic reticulum-associated caspase-4 before the release of mitochondrial apoptogenic factors. Together, our observations indicate that the cardinal function of PC (i.e., Ig secretion) is also the cause of their death.     

Distinct transthyretin oxidation isoform profile in spinal fluid from patients with Alzheimer’s disease and mild cognitive impairment

Background

Transthyretin (TTR), an abundant protein in cerebrospinal fluid (CSF), contains a free, oxidation-prone cysteine residue that gives rise to TTR isoforms. These isoforms may reflect conditions in vivo. Since increased oxidative stress has been linked to neurodegenerative disorders such as Alzheimer’s disease (AD) it is of interest to characterize CSF-TTR isoform distribution in AD patients and controls. Here, TTR isoforms are profiled directly from CSF by an optimized immunoaffinity-mass spectrometry method in 76 samples from patients with AD (n = 37), mild cognitive impairment (MCI, n = 17)), and normal pressure hydrocephalus (NPH, n = 15), as well as healthy controls (HC, n = 7). Fractions of three specific oxidative modifications (S-cysteinylation, S-cysteinylglycinylation, and S-glutathionylation) were quantitated relative to the total TTR protein. Results were correlated with diagnostic information and with levels of CSF AD biomarkers tau, phosphorylated tau, and amyloid β_1-42 peptide.

Results

Preliminary data highlighted the high risk of artifactual TTR modification due to ex vivo oxidation and thus the samples for this study were all collected using strict and uniform guidelines. The results show that TTR is significantly more modified on Cys(10) in the AD and MCI groups than in controls (NPH and HC) (p ≤ 0.0012). Furthermore, the NPH group, while having normal TTR isoform distribution, had significantly decreased amyloid β peptide but normal tau values. No obvious correlations between levels of routine CSF biomarkers for AD and the degree of TTR modification were found.

Conclusions

AD and MCI patients display a significantly higher fraction of oxidatively modified TTR in CSF than the control groups of NPH patients and HC. Quantitation of CSF-TTR isoforms thus may provide diagnostic information in patients with dementia symptoms but this should be explored in larger studies including prospective studies of MCI patients. The development of methods for simple, robust, and reproducible inhibition of in vitro oxidation during CSF sampling and sample handling is highly warranted. In addition to the diagnostic information the possibility of using TTR as a CSF oxymeter is of potential value in studies monitoring disease activity and developing new drugs for neurodegenerative diseases.     

Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State

Background

In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation.

Methodology/Principal Findings

Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-α-stimulated endothelial cells. Nuclear factor kappa B (NF-κB) reporter gene assays confirmed that MOF decrease the activity of NF-κB. Strong inter-individual variability in the leukocytes'' DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found.

Conclusion

Our study revealed that an 8 week daily supplementation with 200 mg MOF modulates the expression of genes associated with cardiovascular disease pathways without major changes of their DNA methylation state. However, strong inter-individual variation in leukocyte DNA methylation may obscure the subtle epigenetic response to dietary flavanols. Despite the lack of significant changes in DNA methylation, the modulation of gene expression appears to contribute to the observed vascular health effect of MOF in humans.     

Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway

The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.     

Amino acid sequence versus morphological data and the interordinal relationships of mammals

To a large extent, the mutual affinities of the mammalian orders continue to puzzle systematists, even though comparative anatomy and amino acid sequencing offer a massive data base from which these relationships could potentially be adduced. In the present paper the consistency index--the number of character states less the number of characters in a data set, divided by the total number of changes in the character states on a cladogram--was used to examine the relative resolving powers of recently published morphological and molecular- sequence data. Consistency indices were calculated for previously published alpha crystallin A chain and myoglobin amino acid-sequence cladograms and for four original amino acid-sequence cladograms (alpha crystallin A, myoglobin, and alpha and beta hemoglobin); these were found to be comparable to the consistency indices of morphologically based cladograms. Qualitative comparisons between the morphologically based and molecularly based trees were also made; only moderate congruence between the two was observed. Moreover, there was a general lack of congruence between the cladograms specified by each of the four proteins. Amino acid-sequence and morphological data agreed on the placement of edentates as an early eutherian offshoot and on the grouping of hyracoids, proboscideans, and sirenians. Otherwise there was only limited congruence: morphology strongly supported the grouping of lagomorphs and rodents and the alliance of pholidotes and edentates, but sequence analyses did not. The placement of tubulidentates differed widely among proteins. Morphology indicated the close association of sirenians with proboscideans; proteins suggested a pairing of sirenians with hyracoids. Sequence data did not identify many (morphologically well-diagnosed) orders as monophyletic (e.g., Lagomorpha).(ABSTRACT TRUNCATED AT 250 WORDS)      

Histological and histochemical study of the uropygial gland of chimango caracara (Milvago chimango vieillot, 1816)

The uropygial glands of birds are sebaceous organs that contribute to the water-repellent properties of the feather coat. We studied the histological and histochemical characteristics of the uropygial gland of chimango caracara using hematoxylin and eosin (H & E), Gomori´s trichrome, orcein, Gomori´s reticulin, periodic acid-Schiff (PAS), Alcian blue (AB) and a variety of lectins. The gland is composed of two lobes and a papilla with 20 downy feathers. It is surrounded by a capsule of dense connective tissue that contains elastic, reticular and smooth muscle fibers. The papilla is delicate and has two excretory ducts. The gland mass relative to body mass was 0.143%. Both adenomer cells and their secretions were stained with Sudan IV, PAS and AB, and were positive for numerous lectins that indicated the presence of lipids and carbohydrates. Immunohistochemical techniques to detect PCNA confirmed cell proliferation in the basal stratum of the adenomer cells. The lipids and glycoconjugates secreted by the uropygial gland serve numerous functions including protection against microorganisms.