Developing human minor salivary glands: morphological parallel relation between the expression of TGF-beta isoforms and cytoskeletal markers of glandular maturation

Morphogenesis of salivary glands involves complex coordinated events. Synchronisation between cell proliferation, polarisation and differentiation, which are dependent on epithelial–mesenchymal interactions and on the microenvironment, is a requirement. Growth factors mediate many of these orchestrated biological processes and transforming growth factor-beta (TGF-beta) appear to be relevant. Using immunohistochemistry and immunofluorescence, we have mapped the distribution of TGF-beta 1, 2 and 3 and compared it with the expression of maturation markers in human salivary glands obtained from foetuses ranging from weeks 4 to 24 of gestation. TGF-beta 1 first appeared during canalisation stage in the surrounding mesenchyme and, in the more differentiated stages, was expressed in the cytoplasm of acinar cells throughout the adult gland. TGF-beta 2 was detected since the bud stage of the salivary gland. Its expression was observed in ductal cells and increased along gland differentiation, TGF-beta 3 was detected from the canalisation stage of the salivary gland, being weakly expressed on ductal cells, and it was the only factor detected on myoepithelial cells. The data suggest that TGF-beta have a role to play in salivary gland development and differentiation.     

CD147 immunohistochemistry discriminates between reactive mesothelial cells and malignant mesothelioma

Malignant mesothelioma (MM) is a rare form of cancer. Its histopathological diagnosis is very difficult, as it exhibits a number of different appearances that can be misinterpreted as metastatic invasion or atypical hyperplasia. Thus, there is an urgent need to identify adequate markers to distinguish between benign and malignant cells, allowing the implementation of appropriate therapies and, possibly, specific directed therapies. MM, like other tumors, show an increase in glucose uptake, due to high rates of glycolysis, inducing an intracellular overload of acids. In this context, monocarboxylate transporters (MCTs) emerge as important players, by mediating the transmembranar co-transport of lactate with a proton, thereby, regulating pH and allowing continuous glycolysis. Importantly, proper MCT expression and activity depend on its co-expression with a chaperone, CD147, which is associated with poor prognosis in cancer. Twenty-two samples including reactive mesothelial cells, MM, and atypical mesothelial hyperplasias were evaluated for immunoexpression of MCT1, MCT4, and CD147. Expression of these proteins was compared with GLUT1 as a new promising marker for MM. Although MCT isoforms were not differentially expressed in the two types of cytological specimens, CD147, as GLUT1, was almost exclusively expressed in MM. Both MCT1 and MCT4 are not able to discriminate between mesothelial reactive cells and mesothelial malignant cells, while CD147 was able to distinguish these two proliferations. If confirmed, besides being a good marker for identification of MM, CD147 may also be a target for therapeutical strategies in this rare type of tumor.     

People with vascular ulcers in outpatient nursing care: a study of sociodemographic and clinical variables

The aim of this study was to analyze the sociodemographic and clinical characteristics of people with vascular ulcers and to investigate the association between these variables. This cross-sectional, observational clinical study was conducted in outpatient clinics from February to August 2009. Interview, clinical exam, Pressure Ulcer Scale Healing and photographic registry of the wounds were performed. Forty-two individuals participated who were, on average, 60 (± 12) years old, 73.8% males, with single wounds (66.7%) resulting from alterations in venous circulation (90.5%). Their wounds had lasted for up to one year (55.5%). There was an association between the PUSH score (p=0.019) and depth of wound (p=0.027) with currently performing occupational activity, as well as between history of tobacco use and gender (p=0.049). The sociodemographic characteristics that were observed were similar to the others, except for being male, which indicates the need for more studies in the population in Goiania, Brazil.     

Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

OBJECTIVES:

Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3⁺ lymphocyte infiltration in differentiated thyroid carcinoma cells.

METHODS:

We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues.

RESULTS:

We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3⁺ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis.

CONCLUSIONS:

We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness.     

Chest computed tomography findings in severe influenza pneumonia occurring in neutropenic cancer patients

OBJECTIVE:

To describe the chest computed tomography findings for severe influenza H1N1 infection in a series of hospitalized neutropenic cancer patients.

METHODS:

We performed a retrospective systematic analysis of chest computed tomography scans for eight hospitalized patients with fever, neutropenia, and confirmed diagnoses of influenza H1N1. The clinical data had been prospectively collected.

RESULTS:

Six of eight patients (75%) developed respiratory failure and required intensive care. Prolonged H1N1 shedding was observed in the three mechanically ventilated patients, and overall hospital mortality in our series was 25%. The most frequent computed tomography findings were ground-glass opacity (all patients), consolidation (7/8 cases), and airspace nodules (6/8 cases) that were frequently moderate or severe. Other parenchymal findings were not common. Five patients had features of pneumonia, two had computed tomography findings compatible with bronchitis and/or bronchiolitis, and one had tomographic signs of chronicity.

CONCLUSION:

In this series of neutropenic patients with severe influenza H1N1 infection, chest computed tomography demonstrated mainly moderate or severe parenchymatous disease, but bronchiolitis was not a common feature. These findings associated with febrile neutropenia should elicit a diagnosis of severe viral infection.     

Is exercise an alternative treatment for chronic insomnia?

The purposes of this systematic/critical review are: 1) to identify studies on the effects of exercise on chronic insomnia and sleep complaints in middle-aged and older adults and to compare the results of exercise with those obtained with hypnotic medications and 2) to discuss potential mechanisms by which exercise could promote sleep in insomniac patients. We identified studies from 1983 through 2011 using MEDLINE, SCOPUS and Web of Science. For systematic analyses, only studies assessing the chronic effects of exercise on sleep in people with sleep complaints or chronic insomnia were considered. We used the following keywords when searching for articles: insomnia, sleep, sleep complaints, exercise and physical activity. For a critical review, studies were selected on the effects of exercise and possible mechanisms that may explain the effects of exercise on insomnia. We identified five studies that met our inclusion criteria for systematic review. Exercise training is effective at decreasing sleep complaints and insomnia. Aerobic exercise has been more extensively studied, and its effects are similar to those observed after hypnotic medication use. Mechanisms are proposed to explain the effects of exercise on insomnia. There is additional documented evidence on the antidepressant and anti-anxiety effects of exercise. Exercise is effective to decrease sleep complaints and to treat chronic insomnia. Exercise presented similar results when compared with hypnotics; however, prospective studies comparing the effects of exercise with medical and non-medical treatments are warranted before including exercise as a first-line treatment for chronic insomnia are necessary.     

Survey of 548 oncogenic fusion transcripts in thyroid tumors supports the importance of the already established thyroid fusions genes

Neoplasms frequently present structural chromosomal aberrations that can alter the level of expression of a protein or to the expression of an aberrant chimeric protein. In the thyroid, the PAX8‐PPARG fusion is present in the neoplastic lesions that have a follicular architecture—follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), and less frequently in follicular thyroid adenoma (FTA), while the presence of RET/PTC fusions are largely restricted to papillary thyroid carcinoma (PTC). The ability to detect fusion genes is relevant for a correct diagnosis and for therapy. We have developed a new fusion gene microarray‐based approach for simultaneous analysis of all known and predicted fusion gene variants. We did a comprehensive screen for 548 known and putative fusion genes in 27 samples of thyroid tumors and three positive controls—one thyroid cancer cell line (TPC‐1) and two PTCs with known CCDC6‐RET (alias RET/PTC1) fusion gene, using this microarray. Within the thyroid tumors tested, only well known, previously reported fusion genes in thyroid oncology were identified. Our results reinforce the pathogenic role played by RET/PTC1, RET/PTC3, and PAX8‐PPARG fusion genes in thyroid tumorigenesis. © 2012 Wiley Periodicals, Inc.     

Cloned tomato golden mosaic virus back in tomatoes

Clones of tomato golden mosaic virus (TGMV), a key model for geminivirus research, have been transmitted back to their original host tomato for the first time. In contrast to the high pathogenicity in other solanaceous species, TGMV induced only very mild symptoms: a few chlorotic spots on the leaf lamina for the common variant (formerly strain cs), and limited vein yellowing for the yellow vein variant (yv). Symptoms disappeared over time, though viral DNA remained detectable in newly developed leaves. Both TGMV variants invaded phloem and, occasionally, also mesophyll parenchyma cells in tomato. Complete direct sequencing of rolling circle amplification products of the viral progeny in tomato plants revealed the consensus of the DNA populations for the two genome components (DNA-A, DNA-B) of both TGMV variants. The DNA-A components showed 98.5% and 99.9% nucleotide sequence identity, respectively, with the independently cloned TGMV molecule sequenced initially in 1984, confirming the classification of csTGMV and yvTGMV as variants. The results are discussed with reference to the history of the Brazilian "mosaico dourado" disease in tomato, and the odyssey of TGMV passaging through Nicotiana benthamiana plants and bacteria of numerous laboratories worldwide.