Loss of breast epithelial marker hCLCA2 promotes epithelial-to-mesenchymal transition and indicates higher risk of metastasis.

Transition between epithelial and mesenchymal states is a feature of both normal development and tumor progression. We report that expression of chloride channel accessory protein hCLCA2 is a characteristic of epithelial differentiation in the immortalized MCF10A and HMLE models, while induction of epithelial-to-mesenchymal transition by cell dilution, TGFß or mesenchymal transcription factors sharply reduces hCLCA2 levels. Attenuation of hCLCA2 expression by lentiviral small hairpin RNA caused cell overgrowth and focus formation, enhanced migration and invasion, and increased mammosphere formation in methylcellulose. These changes were accompanied by downregulation of E-cadherin and upregulation of mesenchymal markers such as vimentin and fibronectin. Moreover, hCLCA2 expression is greatly downregulated in breast cancer cells with a mesenchymal or claudin-low profile. These observations suggest that loss of hCLCA2 may promote metastasis. We find that higher-than-median expression of hCLCA2 is associated with a one-third lower rate of metastasis over an 18-year period among breast cancer patients compared with lower-than-median (n=344, unfiltered for subtype). Thus, hCLCA2 is required for epithelial differentiation, and its loss during tumor progression contributes to metastasis. Overexpression of hCLCA2 has been reported to inhibit cell proliferation and is accompanied by increases in chloride current at the plasma membrane and reduced intracellular pH (pHi). We found that knockdown cells have sharply reduced chloride current and higher pHi, both characteristics of tumor cells. These results suggest a mechanism for the effects on differentiation. Loss of hCLCA2 may allow escape from pHi homeostatic mechanisms, permitting the higher intracellular and lower extracellular pH that are characteristic of aggressive tumor cells.

Effect of iron deficiency anemia on visual evoked potential of growing children.

Iron deficiency anemia is one of the most prevalent yet neglected nutritional deficiencies in the world. Iron is an essential micronutrient and it is ubiquitous in distribution in body. Iron deficiency leads to anemia, hampered physical growth and capacity, and decreased immunoprotective mechanisms. Impairments in cognitive and motor development in children are also seen in iron deficiency. There is increasing number of evidence to support that iron plays important role in central nervous system functions that include synthesis of neurotransmitters and myelination of the nerve. The objective of our study was to observe the effect of iron deficiency anemia on visual evoked potential (VEP) in children between 6 and 24 months of age. The subjects were categorized on the basis of hematological parameters in two groups: iron replete children in the control group (n=25) and iron deplete children in the anemic group (n=25). Iron status of the children was also assessed. Due care was taken to exclude all conditions known to adversely affect the visual evoked potential or the iron status of the children. Flash VEP was studied in all children from each eye individually. In both eyes each of the three waves (N1, P1 and N2) of the flash VEP showed longer latencies (p<0.05) in the anemic group compared with the control group. A negative correlation was found between the severity of iron deficiency anemia and latencies of waves of VEP. Hence, there is a need for prevention and early detection of iron deficiency anemia in growing infants.

Radon, helium and uranium survey in some thermal springs located in NW Himalayas, India: mobilization by tectonic features or by geochemical barriers?

Radon, helium and uranium measurements have been carried out in hot water springs in the Parbati and Beas valleys of Himachal Himalaya. Most of these hot springs are known as famous pilgrimage centers. The activity of dissolved radon in the liquid phase is found to vary widely, by an order of magnitude, between 10 and 750 Bq L(-1), whereas, the dissolved helium content in these thermal springs varies between 10 and 100 ppm. The uranium contents are low and vary from <0.01 to 5 microg L(-1). The measured values of radon, helium and uranium are possibly controlled by structural geology, namely the presence of pervious fault systems, and by the lithology of the leached host rocks. Redox-potential geochemical barriers cause the mobilization of uranile ions in solution (UO2+); the most plausible hypothesis is when the conditions are oxidising, confirming the importance of physico-chemical conditions up to the supergenic environment, to control the fluid geochemistry of the U-He-222Rn system. Some evidence is available from both geothermometric considerations and geochemical data which will be reported elsewhere, whereas the present study is focused on U decay series-noble gas geochemistry. The first analysis of collected 3He/4He data is consistent with a crustal signature at the studied thermal springs.

Cardiovascular reactivity to cold pressor test in offspring of normotensive & hypertensive parents.

A study was undertaken to assess the potential hypertensive status of the offspring of normotensive and hypertensive parents. The volunteers were divided into two groups based on the family history of hypertension. Heart rate and blood pressure recordings were made before and after the cold pressor test. Higher basal values of blood pressure and a significant rise in systolic and diastolic blood pressure in the offspring of hypertensive parents were observed indicating that they have an increased cardiovascular reactivity which was attributed to increased sympathetic activity. Excretion of urinary catecholamines was also found to be significantly higher in about 33 per cent of the offspring of hypertensive parents.

Effect of exercise on pulmonary function tests in normal first degree relations of asthmatic subjects.

The prevalence of exercise-induced asthma (EIA) after six minutes of standard exercise test on bicycle ergometer was studied in thirty healthy first degree relations of asthmatic subjects (group II) and was compared with that in thirty healthy controls (group I). Pulmonary function tests (PFT) measuring FVC, FEV1, FEF25-75% and PEFR were performed on each subject prior of exercise, immediately following exercise period and serially at 5 minute interval for 25 minutes thereafter. Bronchial lability was noted in 7% and 27% of the subjects in groups I and II respectively. Of all the parameters measured, FEF25-75% exhibited most striking changes when expressed as % of the baseline value.