Altered Mucins (MUC) Trafficking in Benign and Malignant Conditions

Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density and activity of important cell membrane proteins (like, receptor tyrosine kinases) to facilitate various signaling, which help cancer cells to proliferate, survive and progress to more aggressive phenotype. In this review article, we summarize studies on mucins trafficking and provide a perspective on its importance to pathological conditions and to answer critical questions including its use for therapeutic interventions.     

Spectrum of pulmonary adenocarcinoma with ultrastructural correlation: an autopsy study from northern India

Background: In the present study, we have evaluated the use of electron microscopy in subtyping pulmonary adenocarcinomas, comparing the ultrastructural findings with the diagnosis rendered by light microscopy. Materials and Methods: The gross and histologic features of 16 autopsy cases of pulmonary adenocarcinoma were analyzed and compared with electron microscopic features. The cytologic phenotypes of these cases of well-differentiated pulmonary adenocarcinoma were determined by electron microscopic examination. More than 200 cells in each case were examined, and the tumors were classified according to the predominant feature noted. Results: Eight cases were of Clara cell origin and one case each of type II pneumocyte and bronchial surface cell type. The remaining 6 cases lacked definite discernible features of differentiation towards any specific cell type, other than presence of small nuclear clefts in occasional nuclei. Tumors with Clara cell differentiation were low cuboidal with apical snouts. Type II pneumocyte tumor failed to reveal any characteristic definable as light microscopic feature. Conclusion: Ultrastructural examination is the only definite means of identification of various cell types in the respiratory epithelium and hence forms an invaluable tool in classification of pulmonary adenocarcinoma.     

CXCR6 identifies a putative population of retained human lung T cells characterised by co-expression of activation markers

Expressions of activation markers have been described on the surface of T cells in the blood and the lung in both health and disease. We have studied the distribution of activation markers on human lung T cells and have found that only certain populations exist. Importantly, the presence or absence of some markers appears to predict those of others, in particular cells which express CD103 also express CD49a and CD69, whereas cells which do not express CD69 also do not express CD49a or CD103. In view of the paucity of activation marker expression in the peripheral blood, we have hypothesised that these CD69+, CD49a+, and CD103+ (triple positive) cells are retained in the lung, possess effector function (IFNgamma secretion) and express particular chemokine receptors which allow them to be maintained in this environment. We have found that the ability of the triple negative cells to secrete IFNgamma is significantly less than the triple positive cells, suggesting that the expression of activation markers can highlight a highly specialised effector cell. We have studied the expression of 14 chemokine receptors and have found that the most striking difference between the triple negative cells and the triple positive cells is the expression of CXCR6 with 12.8+/-9.8% of triple negative cells expressing CXCR6 compared to 89.5+/-5.5% of triple positive cells. We propose therefore that CXCR6 may play an important role in the retention of T cells within the lung.     

Physical Inactivity in Pulmonary Sarcoidosis

Purpose

Reduced physical activity in many chronic diseases is consistently associated with increased morbidity. Little is known about physical activity in sarcoidosis. The aim of this study was to objectively assess physical activity in patients with pulmonary sarcoidosis and investigate its relationship with lung function, exercise capacity, symptom burden, and health status.

Methods

Physical activity was assessed over one week in 15 patients with pulmonary sarcoidosis and 14 age-matched healthy controls with a tri-axial accelerometer (ActivPal™) and the International Physical Activity Questionnaire (IPAQ). All participants underwent pulmonary function tests, 6-min walk test (6MWT) and completed the Fatigue Assessment Scale (FAS), Medical Research Council (MRC) Dyspnoea Scale and the King’s Sarcoidosis Questionnaire (KSQ).

Results

Patients with sarcoidosis had significantly lower daily step counts than healthy controls; mean (SD) 5624 (1875) versus 10,429 (2942) steps (p < 0.01) and a trend towards fewer sit-to-stand transitions each day (p = 0.095). Only two patients (13%) self-reported undertaking vigorous physical activity (IPAQ) compared to half of healthy individuals (p < 0.01). Daily step count was significantly associated with 6MWT distance in sarcoidosis (r = 0.634, p = 0.01), but not with forced vital capacity (r = 0.290), fatigue (r = 0.041), dyspnoea (r = −0.466) or KSQ health status (r = 0.099–0.484). Time spent upright was associated with fatigue (r = −0.630, p = 0.012) and health status (KSQ Lung scores r = 0.524, p = 0.045), and there was a significant correlation between the number of sit-to-stand transitions and MRC dyspnoea score (r = −0.527, p = 0.044).

Conclusion

Physical activity is significantly reduced in sarcoidosis and is associated with reduced functional exercise capacity (6MWD). Fatigue, exertional symptoms and health status were more closely associated with time spent upright and the number of bouts of physical activity, as compared to step counts. Further studies are warranted to identify the factors that determine different physical activity profiles in sarcoidosis.

     

To Snack or Not to Snack: What should we advise for weight management?

Aims: Although our current weight management guidelines suggest eating regularly, speculation about whether snacking assists with managing weight occurs widely among the media, weight loss clients and health professionals. We aim to examine whether there is adequate scientific evidence available to support the manipulation of eating frequently for improving body weight, diabetes and cardiovascular risk markers, and theories that link eating frequently with weight management. Methods: Relevant papers from nutrition and dietetics journals and other sources were used to assess the association between eating frequency and weight and health. Results: Longer‐term evidence suggests eating frequency does not affect weight, glucose, insulin control, hunger or energy expenditure in intentional weight losers and maintainers. There is consistent short‐term evidence of an inverse association between blood lipid levels and eating frequency during weight maintenance. Many of the common theories that suggest manipulating eating frequency for weight management are not supported by the literature. Sustaining a change to eating frequency also may be challenging over the longer term. Conclusions: Overall current evidence does not suggest that manipulating eating frequency greatly benefits weight and health. Health professionals may not need to manipulate eating frequency for weight management.