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Results for “Paradigm shift”

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At least 181 records · Page 10Linked to original sources
PubMed2006

DNA based customized nutraceutical "gene therapy" utilizing a genoscore: a hypothesized paradigm shift of a novel approach to the diagnosis, stratification, prognosis and treatment of inflammatory processes in the human.

We hypothesize that using a multi-variant nutrigenomic index for the purposes of customizing or adjusting the formulation of nutritional supplements will result in an improved and novel approach to the diagnosis, stratification, prognosis, and treatment of inflammatory processes in the human. This multi-variant genetic index, or Genoscore, is derived by analyzing genotype and/or phenotype through measuring multiple genetic mutations of single nucleotide polymorphisms, gene expression, or other forms of genetic and phenotypic measurements. We also propose that manipulation of neurochemical reward circuitry in the mesolimbic brain region providing dopamine release at the nucleus accumbens (NAc), will have both pain and stress relief benefists, which are a cornerstone to the human inflammatory process. This hypothesis, applies to all genes currently discovered or which will be discovered and any nutritional or dietary supplement ingredient currently available or which will become available. For example, if a DNA test was measuring two genes through single nucleotide polymorphisms (Gene A and Gene B), the index scores (Genoscore) that would be reported to the clinician and patient would be based upon the number of mutations. An index score of 0 would mean no mutation. An index score of 1 may mean a mutation in Gene A. An Index Score of 2 may mean a mutation in Gene B. An Index Score of 3 may mean a mutation in Gene A and Gene B, resulting in a simple report, easily understandable to both the clinician and patient that provides insights into disease diagnosis, stratification, prognosis, as well as the metabolism, efficacy and/or toxicity associated with specific vitamins, minerals, herbal supplements, homeopathic ingredients and other ingredients in the nutritional and/or dietary supplement regimen. Furthermore, we have provided support that evidence shows the importance of the dopaminergic connection as an anti-pain and anti-stress molecule, working at the mesocorticolimbic region of the brain, specifically at the NAc. Additionally, we have provided support that clinical evidence demonstrates the effectiveness and safety of natural substances for joint health, such as glucosamine sulfate , chondroitin sulfate, and Ganoderma lucidum.

Dietary Supplements↗
PubMed2004

From interception to incorporation: degeneracy and promiscuous recognition as precursors of a paradigm shift in immunology.

The paper evaluates the role of the concept of degeneracy in current immunology. The historical background of the notion is considered, as well as that of related concepts like 'cross-reactivity' and 'promiscuity'. A distinction is made between degeneracy, as a property of a system and promiscuity, as a property of antibodies and lymphocytes, followed by a discussion of the relation of degeneracy to the clonal selection theory (CST). Attempts to accommodate the notion of degeneracy with the CST theory are critically reviewed. The notion of specific agency is identified as central for this debate, and an alternative conception of the immune response, focused on incorporation rather than interception, is discussed.

Animals↗
PubMed2006

DNA methylation paradigm shift: 15-lipoxygenase-1 upregulation in prostatic intraepithelial neoplasia and prostate cancer by atypical promoter hypermethylation.

Fifteen (15)-lipoxygenase type 1 (15-LO-1, ALOX15), a highly regulated, tissue- and cell-type-specific lipid-peroxidating enzyme has several functions ranging from physiological membrane remodeling, pathogenesis of atherosclerosis, inflammation and carcinogenesis. Several of our findings support a possible role for 15-LO-1 in prostate cancer (PCa) tumorigenesis. In the present study, we identified a CpG island in the 15-LO-1 promoter and demonstrate that the methylation status of a specific CpG within this island region is associated with transcriptional activation or repression of the 15-LO-1 gene. High levels of 15-LO-1 expression was exclusively correlated with one of the CpG dinucleotides within the 15-LO-1 promoter in all examined PCa cell-lines expressing 15-LO-1 mRNA. We examined the methylation status of this specific CpG in microdissected high grade prostatic intraepithelial neoplasia (HGPIN), PCa, metastatic human prostate tissues, normal prostate cell lines and human donor (normal) prostates. Methylation of this CpG correlated with HGPIN, PCa and metastatic human prostate tissues, while this CpG was unmethylated in all of the normal prostate cell lines and human donor (normal) prostates that either did not display or had minimal basal 15-LO-1 expression. Immunohistochemistry for 15-LO-1 was performed in prostates from PCa patients with Gleason scores 6, 7 [(4+3) and (3+4)], >7 with metastasis, (8-10) and 5 normal (donor) individual males. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect 15-LO-1 in PrEC, RWPE-1, BPH-1, DU-145, LAPC-4, LNCaP, MDAPCa2b and PC-3 cell lines. The specific methylated CpG dinucleotide within the CpG island of the 15-LO-1 promoter was identified by bisulfite sequencing from these cell lines. The methylation status was determined by COBRA analyses of one specific CpG dinucleotide within the 15-LO-1 promoter in these cell lines and in prostates from patients and normal individuals. Fifteen-LO-1, GSTPi and beta-actin mRNA expression in BPH-1, LNCaP and MDAPCa2b cell lines with or without 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin-A (TSA) treatment were investigated by qRT-PCR. Complete or partial methylation of 15-LO-1 promoter was observed in all PCa patients but the normal donor prostates showed significantly less or no methylation. Exposure of LNCAP and MDAPCa2b cell lines to 5-aza-dC and TSA resulted in the downregulation of 15-LO-1 gene expression. Our results demonstrate that 15-LO-1 promoter methylation is frequently present in PCa patients and identify a new role for epigenetic phenomenon in PCa wherein hypermethylation of the 15-LO-1 promoter leads to the upregulation of 15-LO-1 expression and enzyme activity contributes to PCa initiation and progression.

Adult↗
PubMed2005

Shifting paradigms: gradient structure in morphology.

Morphology is the study of the internal structure of words. A vigorous ongoing debate surrounds the question of how such internal structure is best accounted for: by means of lexical entries and deterministic symbolic rules, or by means of probabilistic subsymbolic networks implicitly encoding structural similarities in connection weights. In this review, we separate the question of subsymbolic versus symbolic implementation from the question of deterministic versus probabilistic structure. We outline a growing body of evidence, mostly external to the above debate, indicating that morphological structure is indeed intrinsically graded. By allowing probability into the grammar, progress can be made towards solving some long-standing puzzles in morphological theory.

Humans↗
PubMed2004

The significance of focal myoepithelial cell layer disruptions in human breast tumor invasion: a paradigm shift from the "protease-centered" hypothesis.

Human breast epithelium and the stroma are separated by a layer of myoepithelial (ME) cells and basement membrane, whose disruption is a prerequisite for tumor invasion. The dissolution of the basement membrane is traditionally attributed primarily to an over-production of proteolytic enzymes by the tumor or the surrounding stromal cells. The results from matrix metalloproteinase inhibitor clinical trials, however, suggest that this "protease-centered" hypothesis is inadequate to completely reflect the molecular mechanisms of tumor invasion. The causes and signs of ME cell layer disruption are currently under-explored. Our studies revealed that a subset of pre- and micro-invasive tumors contained focal disruptions in the ME cell layers. These disruptions were associated with immunohistochemical and genetic alterations in the overlying tumor cells, including the loss of estrogen receptor expression, a higher frequency of loss of heterozygosity, and a higher expression of cell cycle, angiogenesis, and invasion-related genes. Focal ME layer disruptions were also associated with a higher rate of epithelial proliferation and leukocyte infiltration. We propose the novel hypothesis that a localized death of ME cells and immunoreactions that accompany an external environmental insult or internal genetic alterations are triggering factors for ME layer disruptions, basement membrane degradation, and subsequent tumor progression and invasion.

Basement Membrane↗
PubMed1998

Need for a paradigm shift: the importance of risk factor reduction therapy in treating patients with cardiovascular disease.

Cardiovascular disease remains the number one killer in the United States, despite advances made in diagnosis and therapy. A major shift to expand treatment beyond symptomatic obstructions and infarctions toward comprehensive therapies aimed at treatment of the underlying disease process could decrease the death rate and cost of cardiovascular disease enormously. In the past 5 years, major trials have clearly demonstrated that aggressive intervention with lipid-lowering therapy can dramatically alter the course of disease. Aspirin, smoking cessation, exercise, diet, and other medical and lifestyle interventions can also decrease risk. Successful therapies are not being implemented, however. Making prevention the primary approach to treatment will require increased resource allocation, use of health provider teams, integration of healthcare delivery systems, and expanded emphasis on educating patients about prevention.

Anticholesteremic Agents↗
PubMed1999

Deficit psychopathology and a paradigm shift in schizophrenia research.

Despite recognition that schizophrenia must have syndrome status in the absence of proof of a single etiopathophysiologic process, a century of work has been based on designs that conceptualize schizophrenia as a single disease entity. Reducing heterogeneity at several levels of functioning is desirable. In this article we summarize progress using deficit syndrome psychopathology to address heterogeneity. The deficit syndrome has proven to be reliable, with construct validity, as well as predictive validity with biological, treatment, and course variables. We propose a shift in schizophrenia research away from the syndrome level toward study designs that identify more homogeneous entities. Doing so will increase the statistical power of study designs by reducing false positive cases.

Affect↗
PubMed2000

Paradigm shifts in stem-cell biology.

Hematopoiesis is a physiologic process that can be transplanted by intravenous infusion of stem and progenitor cells. Because these cells contribute to blood production over a lifespan, they are attractive targets for cell-based therapies of hematologic malignancies and genetic defects. A more complete understanding of the basic biology of hematopoiesis will accelerate our progress toward the clinical goal of improved stem-cell-based therapies. Many advances in recent years have brought us closer to that goal and have, in addition, challenged a number of dogmatic notions about hematopoiesis. Three of these advances are briefly addressed here: (1) an emerging appreciation of the complex relationship between cell-cycle status, engraftment potential, and self-renewal in the hematopoietic system; (2) the demonstration of new progenitor populations and lineage relationships in early hematopoietic development; and (3) a reanalysis of the embryonic origins of hematopoiesis. These and other advances are allowing the mysteries of hematopoiesis to be unlocked at a pace that was unimaginable just a few years ago.

Animals↗