Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia

Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and Pan IN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early Pan IN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. Conclusions: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.

The effect of pH on the competition between polyphosphate-accumulating organisms and glycogen-accumulating organisms

In enhanced biological phosphorus removal (EBPR) processes, glycogen-accumulating organisms (GAOs) may compete with polyphosphate-accumulating organisms (PAOs) for the often-limited carbon substrates, potentially resulting in disturbances to phosphorus removal. A detailed investigation of the effect of pH on the competition between PAOs and GAOs is reported in this study. The results show that a high external pH (similar to 8) provided PAOs with an advantage over GAOs in EBPR systems. The phosphorus removal performance improved due to a population shift favouring PAOs over GAOs, which was shown through both chemical and microbiological methods. Two lab-scale reactors fed with propionate as the carbon source were subjected to an increase in pH from 7 to 8. The phosphorus removal and PAO population (as measured by quantitative fluorescence in situ hybridisation analysis of Candidatus Accumulibacter phosphatis) increased in each system, where the PAOs appeared to out-compete a group of Alphaproteobacteria GAOs. A considerable improvement in the P removal was also observed in an acetate fed reactor, where the GAO population (primarily Candidatus Competibacter phosphatis) decreased substantially after a similar increase in the pH. The results from this study suggest that pH could be used as a control parameter to reduce the undesirable proliferation of GAOs and improve phosphorus removal in EBPR systems. (c) 2005 Elsevier Ltd. All rights reserved.

Theoretical and numerical analysis of large-scale heat transfer problems with temperature-dependent pore-fluid densities

Purpose - In many scientific and engineering fields, large-scale heat transfer problems with temperature-dependent pore-fluid densities are commonly encountered. For example, heat transfer from the mantle into the upper crust of the Earth is a typical problem of them. The main purpose of this paper is to develop and present a new combined methodology to solve large-scale heat transfer problems with temperature-dependent pore-fluid densities in the lithosphere and crust scales. Design/methodology/approach - The theoretical approach is used to determine the thickness and the related thermal boundary conditions of the continental crust on the lithospheric scale, so that some important information can be provided accurately for establishing a numerical model of the crustal scale. The numerical approach is then used to simulate the detailed structures and complicated geometries of the continental crust on the crustal scale. The main advantage in using the proposed combination method of the theoretical and numerical approaches is that if the thermal distribution in the crust is of the primary interest, the use of a reasonable numerical model on the crustal scale can result in a significant reduction in computer efforts. Findings - From the ore body formation and mineralization points of view, the present analytical and numerical solutions have demonstrated that the conductive-and-advective lithosphere with variable pore-fluid density is the most favorite lithosphere because it may result in the thinnest lithosphere so that the temperature at the near surface of the crust can be hot enough to generate the shallow ore deposits there. The upward throughflow (i.e. mantle mass flux) can have a significant effect on the thermal structure within the lithosphere. In addition, the emplacement of hot materials from the mantle may further reduce the thickness of the lithosphere. Originality/value - The present analytical solutions can be used to: validate numerical methods for solving large-scale heat transfer problems; provide correct thermal boundary conditions for numerically solving ore body formation and mineralization problems on the crustal scale; and investigate the fundamental issues related to thermal distributions within the lithosphere. The proposed finite element analysis can be effectively used to consider the geometrical and material complexities of large-scale heat transfer problems with temperature-dependent fluid densities.

Temperature and the respiratory properties of whole blood in two reptiles, Pogona barbata and Emydura signata

We investigated the capacity of two reptiles, an agamid lizard Pogona barbata and a chelid turtle Emydura signata, to compensate for the effects of temperature by making changes in their whole blood respiratory properties. This was accomplished by measuring the P-50 (at 10, 20 and 30 degrees C), hematocrit (Hct), haemoglobin concentration ([Hb]) and mean cell haemoglobin concentration (MCHC) in field acclimatised and laboratory acclimated individuals. The acute effect of temperature on P50 in P barbata, expressed as heat of oxygenation (Delta H), ranged from -16.8 +/- 1.84 to -28.5 +/- 2.73 kJ/mole. P-50 of field acclimatised P barbata increased significantly from early spring to summer at the test temperatures of 20 degrees C (43.1 +/- 1.2 to 48.8 +/- 2.1 mmHg) and 30 degrees C (54.7 +/- 1.2 to 65.2 +/- 2.3 mmHg), but showed no acclimation under laboratory conditions. For E. signata, Delta H ranged from -31.1 +/- 6.32 to -48.2 +/- 3.59 kJ/mole. Field acclimatisation and laboratory acclimation of P-50 did not occur. However, in E. signata, there was a significant increase in [Hb] and MCHC from early spring to summer in turtles collected from the wild (1.0 +/- 0.1 to 1.7 +/- 0.2 mmol/L and 4.0 +/- 0.3 to 6.7 +/- 0.7 mmol/L, respectively). (C) 2005 Published by Elsevier Inc.

With the best of intentions: Is it possible to meet the CARI guidelines?

The CARI1 draft dialysis guidelines propose evidence based targets for biochemical and haematological parameters in ESRF. As part of a prospective randomised trial we investigated our ability to apply the CARI and National Heart Foundation of Australia targets to a representative dialysis population. All patients aged between 18–80 yrs were encouraged to enroll regardless of prior history of non-compliance or co-morbidity. Patients were randomised to either usual care (U;n = 44) or focussed care (F;n = 45). Usual care involved monthly blood tests and pysician review second monthly. In addition focus care patients had a monthly review in a physician supervised trial clinic run by nurses. The groups were comparable at baseline in terms of age, gender, dialysis modality, proportion of diabetics, time on dialysis, haemoglobin, ferritin, % saturation, parathyroid hormone, serum corrected calcium, serum phosphate, total cholesterol and LDL. At 6 months there had been significant improvements in PTH (p < 0.05), total cholesterol (p < 0.05) and LDL (p < 0.001), and a trend to better BP control. The proportion of patients meeting targets at 6 months were as follows: tot chol < 5 mmol/l-U 63%, F 82%; LDL < 3 mmol/l-U 75%, F 91%; phosphate < 1.8 mmol/l- U 42%, F 62%; PTH < 21 pmol/l-U 21%, F 40%; BP sys < 140 mmHg-U 41% F 46%; Hb > 11.5 g/dl U 58% F 64%. In spite of an intensive programme to maximise management of the haematological and biochemical parameters in patients with ESRF it appears that in a significant proportion of patients these targets could not be reached. 1The CARI Guidelines (Caring for Australians with Renal Impairment). Australian Kidney Foundation & Australia New Zealand Society of Nephrology, 2001.