			Home About us Contact

Phenotype Differences (phenotype + difference)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Effect of Matrigel on adenoid cystic carcinoma cell line differentiation

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2006
Márcia M. Marques
Summary Adenoid cystic carcinoma (ACC) is a frequent malignant salivary gland neoplasm presenting different growth patterns described as tubular, cribriform and solid, which represent distinct differentiation stages. Cell lines originated from ACCs grown inside three-dimensional environments have not been capable to reproduce all in vivo ACC growth patterns. As ACC cells in vivo present replicated basement membrane, to mimic this situation in vitro ACC cells (CAC2 cells) were grown on the top of a reconstituted basement membrane (Matrigel). Phenotype differences were assessed by light, fluorescence and transmission electron microscopy. The cultures grown on the top of Matrigel presented three-dimensional arrangement of cells intercepted by cellular cords. At these, cell nests pseudocyst formations were observed. This morphological structure entirely reproduced the cribriform growth pattern of ACC. We suggest that the cribriform differentiation of ACC in culture is dependent of proteins and growth factors associated in a bi-dimensional structure. [source]

Nonreplication in Genetic Studies of Complex Diseases,Lessons Learned From Studies of Osteoporosis and Tentative Remedies,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2005
Hui Shen
Abstract Inconsistent results have accumulated in genetic studies of complex diseases/traits over the past decade. Using osteoporosis as an example, we address major potential factors for the nonreplication results and propose some potential remedies. Over the past decade, numerous linkage and association studies have been performed to search for genes predisposing to complex human diseases. However, relatively little success has been achieved, and inconsistent results have accumulated. We argue that those nonreplication results are not unexpected, given the complicated nature of complex diseases and a number of confounding factors. In this article, based on our experience in genetic studies of osteoporosis, we discuss major potential factors for the inconsistent results and propose some potential remedies. We believe that one of the main reasons for this lack of reproducibility is overinterpretation of nominally significant results from studies with insufficient statistical power. We indicate that the power of a study is not only influenced by the sample size, but also by genetic heterogeneity, the extent and degree of linkage disequilibrium (LD) between the markers tested and the causal variants, and the allele frequency differences between them. We also discuss the effects of other confounding factors, including population stratification, phenotype difference, genotype and phenotype quality control, multiple testing, and genuine biological differences. In addition, we note that with low statistical power, even a "replicated" finding is still likely to be a false positive. We believe that with rigorous control of study design and interpretation of different outcomes, inconsistency will be largely reduced, and the chances of successfully revealing genetic components of complex diseases will be greatly improved. [source]

The Campylobacter jejuni stringent response controls specific stress survival and virulence-associated phenotypes

MOLECULAR MICROBIOLOGY, Issue 1 2005
Erin C. Gaynor
Summary Campylobacter jejuni is a highly prevalent food-borne pathogen that causes diarrhoeal disease in humans. A natural zoonotic, it must overcome significant stresses both in vivo and during transmission despite the absence of several traditional stress response genes. Although relatively little is understood about its mechanisms of pathogenesis, its ability to interact with and invade human intestinal epithelial cells closely correlates with virulence. A C. jejuni microarray-based screen revealed that several known virulence genes and several uncharacterized genes, including spoT, were rapidly upregulated during infection of human epithelial cells. spoT and its homologue relA have been shown in other bacteria to regulate the stringent response, an important stress response that to date had not been demonstrated for C. jejuni or any other epsilon-proteobacteria. We have found that C. jejuni mounts a stringent response that is regulated by spoT. Detailed analyses of a C. jejuni,spoT mutant revealed that the stringent response is required for several specific stress, transmission and antibiotic resistance-related phenotypes. These include stationary phase survival, growth and survival under low CO2/high O2 conditions, and rifampicin resistance. A secondary suppressor strain that specifically rescues the low CO2 growth defect of the ,spoT mutant was also isolated. The stringent response additionally proved to be required for the virulence-related phenotypes of adherence, invasion, and intracellular survival in two human epithelial cell culture models of infection; spoT is the first C. jejuni gene shown to participate in longer term survival in epithelial cells. Microarray analyses comparing wild-type to the ,spoT mutant also revealed a strong correlation between gene expression profiles and phenotype differences observed. Together, these data demonstrate a critical role for the C. jejuni stringent response in multiple aspects of C. jejuni biology and pathogenesis and, further, may lend novel insight into unexplored features of the stringent response in other prokaryotic organisms. [source]

Neuroimaging and Cognition in Parkinson's Disease Dementia

BRAIN PATHOLOGY, Issue 3 2010
Lisa C. Silbert MD
Abstract The prevalence of cognitive impairment and dementia in Parkinson's disease (PD) is high and can potentially occur as the result of multiple differing pathologies. Neuroimaging has provided evidence of decreased cortical volume, increased white matter diffusion changes, and decreased resting metabolic activity that appears to begin prior to the onset of dementia in PD patients. Cognitive impairment has been found to be associated with multiple neurotransmitter transmission deficiencies, including dopamine and acetylcholine, indicating a widespread neurotransmitter dysfunction in PD-related dementia. Findings of increased Pittsburgh Compound B (PiB) binding in subjects with Lewy Body Disease (LBD) compared with Parkinson's disease and dementia (PDD) may explain phenotype differences in the spectrum of Dementia with Lewy Bodies (DLB), and show promise in guiding future therapeutic trials aimed at this disease. Advances in neuroimaging now allow for the detection of volumetric, pharmacologic, and pathological changes that may assist in the diagnosis and prediction of cognitive impairment in Parkinson's patients so that better evaluation of disease progression and treatment can be obtained. [source]