Expression of transmembrane carbonic anhydrase isoenzymes IX and XII in normal human pancreas and pancreatic tumours

Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes which are expressed in several epithelia and overexpressed in some carcinomas. They have recently been linked to von Hippel-Lindau gene-mediated carcinogenesis in that both isoenzymes are downregulated by the product of the wild-type von Hippel-Lindau tumour suppressor gene. This paper describes the localisation of CA IX and XII in the normal human pancreas and pancreatic tumours. Both isoenzymes showed positive reaction in the basolateral plasma membrane of the normal acinar and ductal epithelia. The hyperplastic ductal epithelium in tumour specimens generally showed an increased staining for CA IX. Of 29 malignant tumours of exocrine pancreas, 10 showed moderate or strong immunoreaction for CA IX. The signal for CA XII remained weak in most malignant lesions. The present results show that both CA IX and XII are unevenly expressed in the ductal and acinar compartments of the human pancreas. The expression of these isoenzymes in a relatively low number of malignant tumour specimens suggests that they have a limited value in diagnostic evaluation of pancreatic carcinoma. However, the increased expression of CA IX in hyperplastic ductal epithelium may contribute to the pancreatic tumourigenesis.     

FLUCTUATING ASYMMETRY IN CENTRAL AND MARGINAL POPULATIONS OF LYCHNIS VISCARIA IN RELATION TO GENETIC AND ENVIRONMENTAL FACTORS

Developmental instability in the form of increased fluctuating asymmetry can be caused by either genetic or environmental stress. Because extinctions can be attributed broadly to these factors, fluctuating asymmetry may provide a sensitive tool for detecting such stresses. We studied the level of fluctuating asymmetry of flowers of a perennial outcrossing plant species, Lychnis viscaria, both in natural and common-garden populations. The degree of flower asymmetry was higher in small, isolated, and marginal populations of the species range. These marginal populations also were the most homozygous. In the core area of the species' range, flowers were more symmetrical The level of asymmetry was correlated with both population size and heterozygosity. However, a partial correlation analysis revealed that when the impact of population size was controlled for, there was a negative relationship between fluctuating asymmetry and heterozygosity, whereas when controlling for heterozygosity, no relationship between population size and fluctuating asymmetry was found. This indicates that genetic consequences of small population size probably underlie the relationship between the level of asymmetry and population size. Results from a transplantation experiment showed that individuals subjected to a higher environmental stress had an increased level of asymmetry compared to control plants. In the common-garden conditions the level of fluctuating asymmetry did not differ between the central and marginal populations. This suggests that presumably both genetic and environmental factors affected to the higher level of asymmetry among marginal populations compared to central ones. In all we conclude that even though fluctuating asymmetry seems to be a sensitive tool for detecting stresses, results from studies focusing on only one factor should be interpreted with caution.     

Increased Visceral Adipose Tissue as a Potential Risk Factor in Patients with Embolic Stroke of Undetermined Source (ESUS)

Purpose

The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.

Methods

Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered.

Results

Mean VAT area was significantly higher in stroke patients (205±103 cm² for men and 168±99 cm² for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors.

Conclusion

Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.     

[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs

Objective

Inflammation is an important contributor to atherosclerosis progression. A glucose analogue ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [¹⁸F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [¹⁸F]FDG to various stages of coronary plaques in a pig model.

Methods

First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [¹⁸F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).

Results

Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [¹⁸F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).

Conclusions

We found increased uptake of [¹⁸F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [¹⁸F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.     

Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

Background

Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.

Methods

A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.

Results

Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.

Conclusion

IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.     

Genetics of Growth Reaction Norms in Farmed Rainbow Trout

Rainbow trout is farmed globally under diverse uncontrollable environments. Fish with low macroenvironmental sensitivity (ES) of growth is important to thrive and grow under these uncontrollable environments. The ES may evolve as a correlated response to selection for growth in one environment when the genetic correlation between ES and growth is nonzero. The aims of this study were to quantify additive genetic variance for ES of body weight (BW), defined as the slope of reaction norm across breeding environment (BE) and production environment (PE), and to estimate the genetic correlation (r _{g(int, sl)}) between BW and ES. To estimate heritable variance of ES, the coheritability of ES was derived using selection index theory. The BW records from 43,040 rainbow trout performing either in freshwater or seawater were analysed using a reaction norm model. High additive genetic variance for ES (9584) was observed, inferring that genetic changes in ES can be expected. The coheritability for ES was either -0.06 (intercept at PE) or -0.08 (intercept at BE), suggesting that BW observation in either PE or BE results in low accuracy of selection for ES. Yet, the r _{g(int, sl)} was negative (-0.41 to -0.33) indicating that selection for BW in one environment is expected to result in more sensitive fish. To avoid an increase of ES while selecting for BW, it is possible to have equal genetic gain in BW in both environments so that ES is maintained stable.     

Phylogenetic characterisation of Taenia tapeworms in spotted hyenas and reconsideration of the “Out of Africa” hypothesis of Taenia in humans

The African origin of hominins suggests that Taenia spp. in African carnivores are evolutionarily related to the human-infecting tapeworms Taenia solium, Taenia saginata and Taenia asiatica. Nevertheless, the hypothesis has not been verified through molecular phylogenetics of Taenia. This study aimed to perform phylogenetic comparisons between Taenia spp. from African hyenas and the congeneric human parasites. During 2010–2013, 233 adult specimens of Taenia spp. were collected from 11 spotted hyenas in Ethiopia. A screening based on short DNA sequences of the cytochrome c oxidase subunit 1 gene classified the samples into four mitochondrial lineages designated as I–IV. DNA profiles of nuclear genes for DNA polymerase delta (pold) and phosphoenolpyruvate carboxykinase (pepck) showed that lineages II and III can be assigned as two independent species. Common haplotypes of pold and pepck were frequently found in lineages I and IV, suggesting that they constitute a single species. Morphological observations suggested that lineage II is Taenia crocutae, but the other lineages were morphologically inconsistent with known species, suggesting the involvement of two new species. A phylogenetic tree of Taenia spp. was reconstructed by the maximum likelihood method using all protein-coding genes of their mitochondrial genomes. The tree clearly demonstrated that T. crocutae is sister to T. saginata and T. asiatica, whereas T. solium was confirmed to be sister to the brown bear tapeworm, Taenia arctos. The tree also suggested that T. solium and T. arctos are related to two species of Taenia in hyenas, corresponding to lineages I + IV and III. These results may partially support the African origin of human-infecting Taenia spp., but there remains a possibility that host switching of Taenia to hominins was not confined to Africa. Additional taxa from African carnivores are needed for further testing of the “Out of Africa” hypothesis of Taenia in humans.