Coordinated expression of galectin-3 and galectin-3-binding sites in malignant mammary tumors: implications for tumor metastasis

Galectin-3 is a glycan-binding protein that mediates cell-cell and/or cell-extracellular matrix (ECM) interactions. Although galectin-3 is implicated in the progression of various types of cancers, the mechanisms by which galectin-3 enhances metastasis remain unclear. In order to elucidate the role of galectin-3 in the complex multistage process of cancer metastasis, we examined galectin-3 and galectin-3-binding site expression in a series of 82 spontaneous canine mammary tumors (CMT) and two CMT cell lines. Benign CMT tumors exhibited strong nuclear/cytoplasmic galectin-3 immunostaining, whereas malignant CMT tumors and metastases exhibited dramatically decreased galectin-3 expression with the majority of the immunostaining confined to the cytoplasm. Interestingly, intravascular tumor cells overexpressed galectin-3 regardless of their location. CMT-U27 xenografts displayed the same pattern of galectin-3 expression found in spontaneous malignant CMT. In parallel with the downregulation of galectin-3, malignant CMT displayed an overall loss of galectin-3-binding sites in the ECM and focal expression of galectin-3-binding sites mainly detected in intravascular tumor cells and endothelium. Furthermore, loss of galectin-3-binding sites was correlated with the downregulation of GLT25D1, a beta (1-O) galactosyltransferase that modifies collagen, and upregulation of stromal galectin-1. Finally, GLT25D1 mRNA expression was strikingly downregulated in malignant CMT-U27 compared with the benign cell line, and its expression was further de-creased in a galectin-3 knockdown CMT-U27 cell line. We therefore hypothesized that the loss of galectin-3-binding sites in the ECM in conjunction with the overexpression of galectin-3 in specific tumor cell subpopulations are crucial events for the development of mammary tumor metastases.

Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and Prognosis of Endomyocardial Fibrosis Patients

Background-Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. Methods and Results-Thirty-six patients (29 women; age, 54 +/- 12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m(2)). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (P<0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area >19 mL/m(2) had an increased mortality rate, with a relative risk of 10.8. Conclusions-Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.)

Cognitive functioning in subjects with recent-onset psychosis from a low-middle-income environment: Multiple-domain deficits and longitudinal evaluation

Cognitive deficits are a key feature of recent-onset psychosis, but there is no consensus on whether such deficits are generalized or confined to specific domains. Besides, it is unclear whether cognitive deficits: a) are found in psychotic patients in samples from outside high-income countries; and b) whether they progress uniformly over time in schizophrenia and affective psychoses. We applied 12 tests organized into eight cognitive domains, comparing psychosis patients (n = 56, time from initial contact = 677.95+/-183.27 days) versus healthy controls (n = 70) recruited from the same area of Sao Paulo, Brazil. Longitudinal comparisons (digit span and verbal fluency) were conducted between a previous assessment of the subjects carried out at their psychosis onset, and the current follow-up evaluation. Psychosis patients differed significantly from controls on five domains, most prominently on verbal memory. Cognitive deficits remained detectable in separate comparisons of the schizophrenia subgroup and, to a lesser extent, the affective psychosis subjects against controls. Longitudinal comparisons indicated significant improvement in schizophrenia, affective psychoses, and control subjects, with no significant group-by-time interactions. Our results reinforce the view that there are generalized cognitive deficits in association with recent-onset psychoses, particularly of non-affective nature, which persist over time. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Esophageal cancer associated with chronic mucocutaneous candidiasis. Could chronic candidiasis lead to esophageal cancer?

Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and characterized by persistent and refractory infections of the skin, appendages and mucous membranes caused by members of the genus Candida. Several different disorders are classified under this common denominator, including chronic and recurrent mucocutaneous infections due to Candida spp., which are sometimes linked to autoimmune endocrinopathies. These fungal infections are usually confined to the mucocutaneous surface, with little propensity for systemic disease or septicemia. We describe a patient with CMC who had an esophageal candidiasis refractory to treatment for decades and who developed an epidermoid esophageal cancer. No risk factors such as familiar susceptibility, smoking, alcohol drinking, or living in an endemic area were verified. This case report suggests the participation of nitrosamine compounds produced by chronic Candida infections as a risk factor for esophageal cancer in a patient with autosomal-dominant chronic mucocutaneous candidiasis.

Anisotropic Reversible Aggregation of Latex Nanoparticles Suspended in a Lyotropic Nematic Liquid Crystal: Effect of Gradients of Biaxial Order

We studied the anisotropic aggregation of spherical latex particles dispersed in a lyotropic liquid crystal presenting three nematic phases; calamitic, biaxial, and discotic. We observed that in the nematic calamitic phase aggregates of latex particles are formed, which become larger and anisotropic in the vicinity of the transition to the discotic phase, due to a coalescence process. Such aggregates are weakly anisotropic and up to 50 mu m long and tend to align parallel to the director field. At the transition to the discotic phase, the aggregates dissociated and re-formed when the system was brought back to the calamitic phase. This shows that the aggregation is due to attractive and repulsive forces generated by the particular structure of the nematic phase. The surface-induced positional order was investigated by surface force apparatus experiments with the lyotropic system confined between mica surfaces, revealing the existence of a presmectic wetting layer around the surfaces and oscillating forces of increasing amplitude as the confinement thickness was decreased. We discuss the possible mechanisms responsible for the reversible aggregation of latex particles, and we propose that capillary condensation of the N(C) phase, induced by the confinement between the particles, could reduce or remove the gradient of order parameter, driving the transition of aggregates from solidlike to liquidlike and gaslike.

Genetic Polymorphisms of Matrix Metalloproteinases: Susceptibility and Prognostic Implications for Prostate Cancer

Purpose: Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer. Materials and Methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by realtime polymerase chain reaction using TaqMan (R) fluorescent probes. Results: For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042). Conclusions: MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.

Relationship between changes in insulin sensitivity and associated cardiovascular disease risk factors in thiazolidinedione-treated, insulin-resistant, nondiabetic individuals: pioglitazone versus rosiglitazone

This study compared the effects of administering rosiglitazone (RSG) vs pioglitazone (PIO) oil cardiovascular disease risk factors in insulin-resistant. nondiabetic individuals with no apparent disease. Twenty-two nondiabetic, apparently healthy individuals, classified as being insulin resistant oil the basis of a steady-state plasma glucose concentration of at least 10 mmol/L during the insulin suppression test, were treated with either RSG or 1110 for 3 months. Measurements were made before and after drug treatment of weight; blood pressure; fasting and daylong glucose, insulin, and free fatty acid (FFA) levels; and lipid and lipoprotein concentrations. Insulin sensitivity (steady-state plasma glucose concentration) significantly improved in both treatment groups, associated with significant decreases in daylong plasma concentrations of glucose, insulin, and FFA. Diastolic blood pressure fell somewhat in both groups, and this change reached significance in those receiving PIO. Improvement in lipid metabolism was confined to the PIO-treated group, signified by a significant decrease in plasma triglyceride concentration, whereas triglyceride concentration did not decline in the RSG-treated group, and these individuals also had increases in total (P = .047) and low-density lipoprotein cholesterol (P = .07). In conclusion, RSG and PIO appear to have comparable abilities to improve insulin sensitivity and lower daylong glucose, insulin, and FFA concentrations in nondiabetic, insulin-resistant individuals. However, despite these similarities, their effects on lipoprotein metabolism seem to be quite different, with beneficial effects confined to PIO-treated individuals. (C) 2009 Elsevier Inc. All rights reserved.

Accuracy of direct digital radiography for detecting occlusal caries in primary teeth compared with conventional radiography and visual inspection: an in vitro study

Objectives: The diagnosis of caries lesions is still a matter of concern in dentistry. The diagnosis of dental caries by digital radiography has a number of advantages over conventional radiography; however, this method has not been explored fully in the field of paediatric dentistry. This in vitro research evaluated the accuracy of direct digital radiography compared with visual inspection and conventional radiography in the diagnosis of occlusal caries lesions in primary molars. Methods: 50 molars were selected and evaluated under standardized conditions by 2 previously calibrated examiners according to 3 diagnostic methods (visual inspection, conventional radiography and direct digital radiography). Direct digital radiographs were obtained with the Dixi3 system (Planmeca, Helsinki, Finland) and the conventional radiographs with InSight film (Kodak Eastman Co., Rochester, NY). The images were scored and a reference standard was obtained histologically. The interexaminer reliability was calculated using Cohen`s kappa test and the specificity, sensitivity and accuracy of the methods were calculated. Results: Examiner reliability was good. For lesions limited to the enamel, visual inspection showed significantly higher sensitivity and accuracy than both radiographic methods, but no significant difference was found in specificity. For teeth with dentinal caries, no significant differences were found for any parameter when comparing visual and radiographic evaluation. Conclusions: Although less accurate than the visual method for detecting caries lesions confined to the enamel, the direct digital radiographic method is as effective as conventional radiographic examination and visual inspection of primary teeth with occlusal caries when the dentine is involved. Dentomaxillofacial Radiology (2010) 39, 362-367. doi: 10.1259/dmfr/22865872

Does workforce participation empower women? Micro-level evidence from urban Bangladesh

Empirical studies on the impact of women’s paid jobs on their empowerment and welfare in the Bangladesh context are rare. The few studies on the issue to date have all been confined to the garment workers only although studies indicate that women’s workforce participation in Bangladesh has increased across-the-board. Besides, none of these studies has made an attempt to control for the non-working women and/or applied any statistical technique to control for the effects of other pertinent determinants of women’s empowerment and welfare such as education, age, religion and place of living. This study overcomes these drawbacks and presents alternative assessments of the link between women’s workforce participation and empowerment on the basis of survey data from the two largest cities in Bangladesh. While the generic assessment indicates that women’s paid jobs have positive implications for women’s participation in decisions on fertility, children’s education and healthcare as well as their possession and control of resources, the econometric assessment negates most of these observations. Women’s education, on the other hand, appears to be more important than their participation in the labour force. The study underlines the fact that by omitting other relevant explanatory variables from the analysis, the previous studies might have overestimated the impact of women’s paid work on their empowerment. Among other things, the paper also highlights the importance of women’s job category, religion and regional differences for women’s empowerment.

A nanometre-scale non-periodic structural variation in high temperature superconducting ceramics and the implications for properties

Non-periodic structural variation has been found in the high T-c cuprates, YBa2Cu3O7-x and Hg0.67Pb0.33Ba2Ca2Cu3O8+delta, by image analysis of high resolution transmission electron microscope (HRTEM) images. We use two methods for analysis of the HRTEM images. The first method is a means for measuring the bending of lattice fringes at twin planes. The second method is a low-pass filter technique which enhances information contained by diffuse-scattered electrons and reveals what appears to be an interference effect between domains of differing lattice parameter in the top and bottom of the thin foil. We believe that these methods of image analysis could be usefully applied to the many thousands of HRTEM images that have been collected by other workers in the high temperature superconductor field. This work provides direct structural evidence for phase separation in high T-c cuprates, and gives support to recent stripes models that have been proposed to explain various angle resolved photoelectron spectroscopy and nuclear magnetic resonance data. We believe that the structural variation is a response to an opening of an electronic solubility gap where holes are not uniformly distributed in the material but are confined to metallic stripes. Optimum doping may occur as a consequence of the diffuse boundaries between stripes which arise from spinodal decomposition. Theoretical ideas about the high T-c cuprates which treat the cuprates as homogeneous may need to be modified in order to take account of this type of structural variation.

Timely topic: Premalignant lesions associated with adenocarcinoma of the upper gastrointestinal tract

The changing incidence of adenocarcinomas, particularly in the oesophagus and gastric cardia, has led to the rapid expansion of screening programmes aimed at detecting the precursor lesion of dysplasia before adenocarcinoma develops. The pathologist now has an important role in first diagnosing patients at risk for developing dysplasia, and then correctly classifying dysplasia when it occurs. Barrett's oesophagus has had different diagnostic criteria in previous years but is currently diagnosed by the presence of intestinal metaplasia of any length in the true oesophagus. Intestinal metaplasia confined only to the gastro-oesophageal junction or cardia is of uncertain significance but is probably common, with less risk of progressing to dysplasia or malignancy. In the stomach, patients with autoimmune atrophic gastritis and Helicobacter-associated multifocal atrophic gastritis have an increased risk of adenocarcinoma, but screening protocols are not well-developed compared with those used for Barrett's oesophagus. Dysplasia of glandular epithelium can be classified using well-described criteria. Low grade dysplasia is the most common type and regresses or remains stable in the majority of patients. High grade dysplasia is more ominous clinically, with a propensity to coexist with or progress to adenocarcinoma.

Long-term risk stratification for survivors of acute coronary syndromes - Results from the long-term intervention with pravastatin in ischemic disease (LIPID) study

OBJECTIVES We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS). BACKGROUND Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting. METHODS Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes. RESULTS In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% fur those assigned placebo. CONCLUSIONS Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy. CT Am Coil Cardiol 2001;38:56-63) (C) 2001 by the American College of Cardiology.

Emmetropization in chicks uses optical vergence and relative distance cues to decode defocus

When visual information is confined to one object plane, the emmetropization end-point is adjusted in accord with the corresponding incident optical vergence at the eye [Proceedings of the 7th International Conference on Myopia (2000) 113]. We now report the effect of adding extra visual information beyond the target plane. Visual conditions were controlled using a cone-lens system: black Maltese cross targets on white opaque backgrounds (OMX) were attached to the open faces of 2.5 cm translucent cones fitted with either 0, +25 or +40 D imaging lenses. An alternative target (TMX) was made by substituting the opaque target background for a transparent background, which allowed access to visual information beyond the target plane. The imaging devices were applied to 7-day-old chicks and worn for 4 days. Prior to this treatment, on day 2, some chicks underwent ciliary nerve section (CNS) to preclude accommodation. All treatments were monocular. Refractive errors and axial ocular dimensions were measured using retinoscopy and A-scan ultrasonography under halothane anesthesia. Treatment effects were specified as mean ( +/-S.D.) interocular differences. Eyes with the OMX/ + 40 D lens combination remained emmetropic ( +0.73 +/-3.57 D), consistent with the target plane being approximately conjugate with the retina. Switching to the TMX caused a hyperopic shift in refractive error ( + 3.78 +/- 3.41 D). This relative shift towards hyperopia in switching from the OMX to the TMX target also occurred for the other two lens powers. Thus, the OMX/ + 25 D lens induced myopia ( - 7.00 +/-5.88 D), corresponding to the imposed hyperopic defocus (target plane now imaged behind the retina), and switching to the TMX resulted in a reduction in myopia (-1.73 +/-5.36 D), The OMX/0 D lens combination produced the largest myopic shift, and here, switching to the TMX condition almost eliminated the myopic response (-15.50 +/-6.62 D cf. -0.56 +/-1.24 D). This relative hyperopic shift associated with switching from the OMX to the TMX target was eliminated by CNS surgery. Thus, the two CNS/TMX groups were both more myopic than the equivalent no CNS/TMX groups ( + 40 D lens: -2.66 +/-2.34 D; +25 D lens: -7.97 +/-6.87 D). When the visual information is restricted to one plane, incident optical vergence appears to direct emmetropization. Adding Visual information at other distances produces a shift in the end-point of ernmetropization in the direction of the added information. That these effects are dependent on the integrity of the accommodation system implies that accommodation plays a role in emmetropization and represents the first reported evidence of this kind. Published by Elsevier Science Ltd.

Optically driven micromachine elements

We report on a proof of principle demonstration of an optically driven micromachine element. Optical angular momentum is transferred from a circularly polarized laser beam to a birefringent particle confined in an optical tweezers trap. The optical torque causes the particle to spin at up to 350 Hz, and this torque is harnessed to drive an optically trapped microfabricated structure. We describe a photolithographic method for producing the microstructures and show how a light driven motor could be used in a micromachine system. (C) 2001 American Institute of Physics.

Heat of desorption measured by means of electrical heat excitation

A new method of measuring heat of desorption is proposed in this Letter. The principle of the method is to measure the amount of mass released when a controlled amount of energy is supplied directly to a solid adsorbent. This is in contrast to conventional methods such as microcalorimetry, where heat released upon adsorption is measured. In this method, a quantified heat supply is generated by passing a de current through a carbon pellet, which is equilibrated with a gas phase confined in a closed vessel. As a consequence of the heating, the particle temperature is increased, resulting in partial desorption of adsorbed molecules. The variations of pellet temperature and the system pressure with respect to time are used to determine the heat of desorption as a function of loading.