Def of disease
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Defining Disease: Philosophical and Clinical Perspectives
Philosophical Definition of Disease
The philosophical definition of disease has been a subject of debate among scholars. Boorse's definition, which describes disease as an impairment or limitation of normal function, has been influential but also criticized for its clinical impracticality. Temple and co-authors argue that this definition does not adequately address the complexities of disease in the genomics era, suggesting that a more nuanced approach is necessary to capture the multifaceted nature of disease1.
Quantitative Metrics in Disease Evaluation
In the realm of clinical practice, quantitative metrics are essential for assessing disease burden and progression. For instance, in Alzheimer's disease (AD), researchers have developed a Disease Evaluation Factor (DEF) to quantitatively measure disease burden. This metric uses MRI data to distinguish between normal control subjects and probable AD patients with an accuracy of 87%. Such quantitative biomarkers are crucial for tracking disease status and progression, providing a more objective and precise method of evaluation2.
Automated Segmentation in Neurodegenerative Diseases
Advancements in imaging technology have also contributed to better disease definition and monitoring. Automated segmentation methods, such as the Classification using DErivative-based Features (C-DEF), have been developed to improve the accuracy of brain MRI segmentation. This method has shown superior performance in detecting lesions in various neurological diseases compared to traditional methods. Improved segmentation techniques help in understanding the relationship between imaging abnormalities and clinical markers, thereby enhancing disease definition and management3.
Genetic and Molecular Insights
On a molecular level, the study of specific proteins and genes provides deeper insights into disease mechanisms. For example, the Protein Def, related to alpha1 immunoglobulin heavy chain, is characterized by an internal deletion and postsynthetic modifications. Understanding such molecular anomalies helps in defining diseases at a genetic level, which is crucial for developing targeted therapies4.
Genetic Variability and Disease Susceptibility
Genetic variability plays a significant role in disease susceptibility and progression. The DEF locus on chromosome 8p23.1, which contains defensin genes, exhibits high structural dynamics and genetic variations. These variations can influence the assembly of the human reference genome and impact disease susceptibility. Comparative studies between humans and chimpanzees have shown differences in DEF genes that may contribute to varying disease susceptibilities between species5.
Influence of Innate Immunity Genes
Polymorphisms in innate immunity genes, such as Toll-like receptors (TLRs) and defensins (DEFs), can significantly influence disease progression. In HIV-1-infected children, specific polymorphisms in TLR9 and DEF&bgr;1 genes have been associated with different clinical outcomes. These genetic variations can either accelerate disease progression or correlate with better clinical outcomes, highlighting the importance of genetic factors in disease definition and management6.
Conclusion
Defining disease is a complex task that requires a multifaceted approach, incorporating philosophical perspectives, quantitative metrics, advanced imaging techniques, and genetic insights. By integrating these diverse elements, we can achieve a more comprehensive and precise understanding of disease, ultimately leading to better diagnosis, monitoring, and treatment strategies.
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The Challenge of Defining Disease
The philosophical definition of disease based on impairment or limitation of normal function that Boorse ([1][1]) proposed is rejected as being clinically impractical by L. K. F. Temple and co-authors in their Essay “Defining disease in the genomics era” ( Science 's Compass, 3 Aug., p. [807][2
Quantitative evaluation of Alzheimer's disease
The disease evaluation factor (DEF) accurately separates normal, control subjects from probable Alzheimer's disease patients with 87% accuracy, making it a potential surrogate marker for disease status and progression.
Observational StudyRobust, atlas-free, automatic segmentation of brain MRI in health and disease
C-DEF outperforms other segmentation algorithms in various neurological diseases, especially in lesion detection, and can be easily trained and optimized for wider application.
Observational Study"Alpha chain disease" protein def: internal deletion of a human immunoglobulin A1 heavy chain.
Protein Def is a human alpha chain disease protein synthesized as an internally deleted alpha1 heavy chain, with valine residues in the hinge region potentially acting as a recognition site for reinitiating synthesis after internal gaps.
Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence
Complexity and variability in the human DEF locus at 8p23.1 pose challenges for accurate representation in the human reference sequence, and future studies should focus on interindividual variability and its disease association.
Polymorphisms of innate immunity genes influence disease progression in HIV-1-infected children
TLR9 1635AG genotype and [G;G] haplotype are associated with rapid disease progression in HIV-1-infected children, while DEF&bgr;1 44CG genotype and [G;G] haplotype are associated with better clinical outcome.
Observational Study
Rigorous JournalDEF6 deficiency, a mendelian susceptibility to EBV infection, lymphoma and autoimmunity.
DEF6 deficiency is a new inherited immune dysregulation disorder with variable expressivity, ranging from autoimmunity to EBV-associated viremia/lymphoproliferation/lymphoma without extra-hematopoietic manifestations.
Case ReportRigorous JournalMast cell activation disease and immunoglobulin deficiency in patients with hypermobile Ehlers‐Danlos syndrome/hypermobility spectrum disorder
Mast cell activation disease and immunoglobulin deficiency are common comorbidities in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder, highlighting the need for personalized therapies to reduce tissue damage and optimize health outcomes.
Observational StudyTwo novel defensin-encoding genes of the Chagas disease vector Triatoma brasiliensis (Reduviidae, Triatominae): gene expression and peptide-structure modeling.
Two novel defensin-encoding genes (def3 and def4) in Triatoma brasiliensis were identified, with cationic structures and tissue-specific expression, potentially targeting distinct microorganisms in different organs.
HLA linkage and B14, DR1, BfS haplotype association with the genes for late onset and cryptic 21-hydroxylase deficiency.
Late onset and cryptic 21-hydroxylase deficiency are both HLA-linked, suggesting they may represent different clinical expressions of similar or identical nonclassical 21-OH-def alleles.
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