Interleukins 4 and 13 upregulate expression of cd44 in human colonic epithelial cell lines

Interleukin 4 (IL-4) inhibits carcinoma cell growth and promotes expression of differentiation-associated products by normal and malignant epithelial cells. The effects of IL-4 and IL-13 on expression of the CD44 transmembrane adhesion receptor were examined in human epithelial cell lines of colonic (HT-29, CaCo-2, DLD-1, T84), breast (MCF-7, ZR75-1) and liver (Hep-G2, PLC/PRF/5) origins as well as mitogen-activated and resting peripheral blood lymphocytes (PBL) and T cell lines (Jurkat, HUT78). Liver and Jurkat cells were negative for CD44. Colonic, breast and HUT78 cells expressed CD44 constitutively and all except DLD-1 and HUT78 also expressed CD44 splice variant (CD44v) epitopes. All cell lines expressed IL-4 receptors, but IL-4 and IL-13 induced upregulation of CD44 only in the colonic cell lines. CD44v was also upregulated, but there was no de novo induction of CD44v in variant-negative cells and no de novo expression of CD44 in the CD44(-) lines. CD44 upregulation in mitogen-activated PBL was not increased by IL-4 and IL-13 and was not inhibited by neutralizing antibodies. Other cytokines tested [interferon gamma (IFN-gamma, tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1) and IL-6] did not affect CD44 core epitope expression in the cell lines tested.     

Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain

Adenovirus-mediated gene transfer into the brain is associated with significant inflammation and activation of anti-vector and anti-transgene immune responses that curtail the gene delivery of adenoviruses and therapeutic efficacy. Elucidating the molecular mediators of inflammatory and immune responses to adenoviruses injected into the brain should allow us to inhibit their inflammatory actions, thereby reducing vector clearance and enhance adenoviral-mediated gene transfer into the CNS. Cytokines are primary mediators of the immune response and are released during inflammation. Here we report for the first time that injection of replication-deficient adenovirus vectors into the cerebral ventricles of rats causes a rapid increase in body temperature. This fever response precedes any vector-encoded transgene expression and occurs with vectors encoding no transgene, as well as with vectors encoding a therapeutic transgene i.e., HSV1-thymidine kinase. No fever is detected after infection of the striatum, an important brain target in studies on neurodegeneration. After infection of the brain ventricles, CSF levels of immunoreactive tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta increase significantly (up to 300-fold). In the hypothalamus, the locus of thermoregulation in the brain, only IL-1beta and IL-6 are significantly elevated. A neutralizing TNF-alpha antibody has no effect on adenovirus-induced fever. However, pretreatment with either the IL-1 receptor antagonist or the cyclooxygenase inhibitor flurbiprofen completely abolishes adenovirus-induced fever, suggesting that IL-1 and prostaglandins are direct mediators of this response. These results are the first to demonstrate that IL-1, but not TNF-alpha, is the main mediator of a very early inflammatory response to adenovirus in the brain.     

Searching beneath the shelf in macaque monkeys: Evidence for a gravity bias or a foraging bias?

The reasons underpinning search biases in 2 species of macaque monkeys (Macaca mulatta and Macaca arctoides) were explored over the course of 3 experiments requiring monkeys to search for a hidden food reward. The results reveal that monkeys are adept at exploiting perceptual cues to locate a food reward but are unable to use physical constraints such as solidity as cues to the reward's location. Monkeys prefer to search for a food reward beneath a solid shelf, not because they have an expectation that the reward should be there, but rather because, in the absence of usable cues, this bias emerges as a default search option. It is hypothesized that this bias may have its roots in a history of competition for food resources. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of a differentiated ciliated cell phenotype in primary cultures of Fallopian tube epithelium

Human Fallopian tubal epithelial cells in culture lose morphological features associated with the epithelium in situ and the extent to which they retain their in-vivo phenotype or function is unknown. In order to address this question, immunocytochemical markers were identified which distinguish secretory (HMFG2+, LhS28-) from ciliated (HMFG2-, LhS28+) epithelial cells in tissue sections of Fallopian tube. These markers were used to analyse the phenotype of tubal cells in vitro. Primary cultures of human tubal epithelial cells were seeded onto glass and grown to confluence before addition of oestradiol-17beta. In the absence of hormone, tubal epithelial cells expressed cytokeratins and nuclear receptors for oestrogen and progesterone and adopted a homogeneous (HMFG2+, LhS28-) secretory cell phenotype. Following the addition of oestradiol-17beta, a proportion of cells became positive for LhS28. The induction of a ciliated epithelial cell phenotype was confirmed by scanning electron microscopy, where on permeable collagen membranes, approximately one-third of tubal epithelial cells became ciliated in the presence of oestradiol-17beta. We suggest that in vitro, tubal epithelial cells adopt an immature secretory-like phenotype and that oestrogen can induce differentiation to a ciliated epithelial cell phenotype.     

Cytokeratin 20 as an objective marker of urothelial dysplasia

OBJECTIVE: To investigate the dysregulation of cytokeratin 20 (CK20) expression in urothelial dysplasia and its potential as a diagnostic aid. PATIENTS AND METHODS: Twenty-two patients were selected on the basis that they had undergone one or more biopsies showing dysplasia before the development of a transitional cell carcinoma (TCC): 15 of these patients also had a prior history of TCC. The dysplasia was classified as mild in 12, moderate in 14 or severe dysplasia/carcinoma in situ in 10 patients, ensuring that a spectrum of morphological appearances was represented. Control biopsies were obtained from seven children undergoing bladder reconstructions and 23 patients with recurrent urinary tract infections, haematuria or functional bladder symptoms, but no history of TCC. RESULTS: The expression of CK20 was restricted to superficial 'umbrella' cells and occasional intermediate cells in the control biopsies, even in the presence of severe inflammation. In 31 of the 36 cases of dysplasia complete loss of restriction was seen at least focally with positive expression in all layers of the urothelium. CONCLUSION: The abnormal expression of CK20 is a reliable, positive marker of urothelial dysplasia in the urinary bladder. Immunostaining for CK20 is therefore a useful adjunct to morphology in the diagnosis of dysplasia, of particular value in the distinction from reactive states where diagnostic difficulties are greatest.     

Determination of carbohydrates in foods. II. Unavailable carbohydrates

A fractionation and analytical procedure is described for the measurement of the unavailable carbohydrates in foods. The scheme provides values for water-soluble polysaccharides, hemicellulose, cellulose and lignin. Tests used to investigate the reliability of the methods are reported and the results obtained with a range of foodstuffs are presented. From the results obtained it is possible to derive values for the composition of the cell-wall material of these foods. The results are in agreement with more detailed studies of the composition of the cell walls of plants.     

Recent studies on the reproductive biology of the schistosomes and their relevance to speciation in the Digenea

The members of the family Schistosomatidae, dioecious Digenea, are discussed with regard to their distribution, intermediate and definitive host-parasite relationships. The biological species concept is considered together with the difficulties of its application to Schistosoma spp. and the Digenea. The correlation between pairing of adult schistosomes, physical and sexual development and the maintenance of reproductive potential is emphasised. Development of the female reproductive system does not depend upon species-specific pairing. In some combinations, e.g., Schistosoma haematobium/Schistosoma intercalatum and Schistosoma bovis/Schistosoma curassoni, a specific mate choice system apparently does not exist, whereas it does in other combinations, e.g., Schistosoma mansoni/Schistosoma intercalatum. In mixed infections change of mate may occur and when the opportunity arises heterospecific pairs of worms will change partners to conspecific pairs. Interspecific pairing in adult schistosomes will lead to either hybridisation or parthenogenesis. Yet the majority of schistosomes that inhabit the same definitive host maintain their genetic identity: specific mate recognition, site selection within the host and heterologous immunity have been suggested as isolating mechanisms. Experimental intraspecific crosses have enabled evaluation of the degree to which some populations separated and became reproductively isolated through pre-mating isolating mechanisms, indicative of incipient speciation, e.g., the Lower Guinea and Zaire strains of S. intercalatum. The occurrence and significance of parthenogenesis in schistosomes and other species of Digenea are discussed. The consequences of interspecific mating interactions in schistosomes with regard to parasite epidemiology, interspecific competition and genetic heterogeneity are debated. Geographical isolation and host specificity represent important pre-zygotic isolating mechanisms. It is suggested that site selection within the host and heterologous immunity may both reduce interspecific genetic interchange when digenean parasites utilise the same definitive host.