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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Pathology

  • These data indicate that relaxin may be efficacious in the treatment of pathologies characterized by lung fibrosis [1].
  • This Review will focus on the mechanisms of action of PPARalpha in metabolic diseases and their associated vascular pathologies [2].
  • Here, Christian Engwerda and Paul Kaye highlight the importance of defining organ-specific immune mechanisms for developing strategies that deal effectively with infectious diseases and their associated pathologies [3].
  • This knowledge may lead to a better assessment of the possible role of 5-HT in cardiovascular pathologies and to the development of selective 5-HT receptor agonists and antagonists for therapeutic usefulness in heart failure, coronary vasospasm and to avoid potential cardiac side-effects [4].
  • Latent membrane protein 2 (LMP2) is expressed both in normal EBV latency and EBV-associated pathologies [5].

Psychiatry related information on Pathology


High impact information on Pathology

  • Our knowledge of SMPD3 function is consistent with the pathology observed in mutant mice and provides new insight into human pathologies [11].
  • The protease region is not affected by the endogenous inhibitor, calpastatin, and may contribute to calpain-mediated pathologies when the core is released by autoproteolysis [12].
  • Mutations of the Wilms'-tumour gene, WT1, cause different pathologies of the urogenital system, including DDS [13].
  • We generated mice deficient in Plg and fibrinogen (Fib) and show that removal of fibrin(ogen) from the extracellular environment alleviates the diverse spontaneous pathologies previously associated with Plg deficiency and corrects healing times [14].
  • These observations elucidate a potential role for vpr in the virus life cycle and raise the possibility that some aspects of HIV-induced pathologies may be caused by a disturbance of cells by vpr [15].

Chemical compound and disease context of Pathology


Biological context of Pathology

  • Akt kinases control essential cellular functions, including proliferation, apoptosis, metabolism and transcription, and have been proposed as promising targets for treatment of angiogenesis-dependent pathologies, such as cancer and ischemic injury [21].
  • Caspase-8 deficiency is associated with pathologies that are unexpected for a proapoptotic molecule, such as abrogation of activation-induced lymphocyte proliferation, perturbed immune homeostasis, and immunodeficiency [22].
  • We examined Bdnf conditional mutant mice for RTT-relevant pathologies and observed that loss of BDNF caused smaller brain size, smaller CA2 neurons, smaller glomerulus size, and a characteristic hindlimb-clasping phenotype [23].
  • This study shows that fibrin deposition exacerbates axonal injury, and that induction of an extracellular proteolytic cascade is a beneficial response of the tissue to remove fibrin. tPA/plasmin-mediated fibrinolysis may be a widespread protective mechanism in neuroinflammatory pathologies [24].
  • The LMNA gene encoding two nuclear envelope proteins (lamins A and C [lamin A/C]) maps to chromosome 1q21 and has been associated with five distinct pathologies, including Dunnigan-type familial partial lipodystrophy, a condition that is characterized by subcutaneous fat loss and is invariably associated with insulin resistance and diabetes [25].

Anatomical context of Pathology


Associations of Pathology with chemical compounds

  • Our data suggest that TNF-alpha processing is mediated by a unique Zn2+ endopeptidase which is inhibited by GI 129471 and would represent a novel target for therapeutic intervention in TNF-alpha associated pathologies [31].
  • Tumor necrosis factor (TNF) is a central mediator of a number of important pathologies such as the systemic inflammatory response syndrome [32].
  • Activation through Ca(2+) explains sensitivity to lactate, which decreases extracellular [Ca(2+)], and it may prove relevant in CNS pathologies (stroke, seizure) that simultaneously drop pH and Ca(2+) [33].
  • To determine in vivo how unbalanced expression of these factors can promote or affect the course of pathologies, we knocked out the mouse gelatinase B gene by replacing the catalytic and zinc-binding domains with an antisense-oriented neomycin resistance gene [34].
  • We hypothesized that adenosine accumulation, alterations in adenosine receptors, and adenosine-IL-13 autoinduction are critical events in IL-13-induced pathologies [35].

Gene context of Pathology

  • This provides the first direct evidence in vivo that RANTES has significant proinflammatory activity and, in addition, could be a mediator in atopic pathologies characterized by eosinophilic and monocytic inflammatory responses [36].
  • These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation [37].
  • JAM-3 thereby provides a novel molecular target for antagonizing interactions between vascular cells that promote inflammatory vascular pathologies such as in atherothrombosis [38].
  • PrP(C)-deficient mice do not exhibit major pathologies, perhaps because they express a protein termed Dpl, which shares significant biochemical and structural homology with PrP(C) [39].
  • Furin, the best-characterized member of the mammalian PC family, has essential functions in embryogenesis and homeostasis but is also implicated in various pathologies such as tumor metastasis, neurodegeneration and various bacterial and viral diseases caused by such pathogens as anthrax and pathogenic Ebola virus strains [40].

Analytical, diagnostic and therapeutic context of Pathology


  1. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. Unemori, E.N., Pickford, L.B., Salles, A.L., Piercy, C.E., Grove, B.H., Erikson, M.E., Amento, E.P. J. Clin. Invest. (1996) [Pubmed]
  2. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. Lefebvre, P., Chinetti, G., Fruchart, J.C., Staels, B. J. Clin. Invest. (2006) [Pubmed]
  3. Organ-specific immune responses associated with infectious disease. Engwerda, C.R., Kaye, P.M. Immunol. Today (2000) [Pubmed]
  4. 5-Hydroxytryptamine: a chameleon in the heart. Saxena, P.R., Villalón, C.M. Trends Pharmacol. Sci. (1991) [Pubmed]
  5. Epstein-Barr virus latency: LMP2, a regulator or means for Epstein-Barr virus persistence? Longnecker, R. Adv. Cancer Res. (2000) [Pubmed]
  6. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Lewis, J., Dickson, D.W., Lin, W.L., Chisholm, L., Corral, A., Jones, G., Yen, S.H., Sahara, N., Skipper, L., Yager, D., Eckman, C., Hardy, J., Hutton, M., McGowan, E. Science (2001) [Pubmed]
  7. Clinicopathological correlates in frontotemporal dementia. Hodges, J.R., Davies, R.R., Xuereb, J.H., Casey, B., Broe, M., Bak, T.H., Kril, J.J., Halliday, G.M. Ann. Neurol. (2004) [Pubmed]
  8. Multiple roles of protein kinases in the modulation of gamma-aminobutyric acid(A) receptor function and cell surface expression. Brandon, N., Jovanovic, J., Moss, S. Pharmacol. Ther. (2002) [Pubmed]
  9. Intra-individual differences between technetium-99m-HMPAO and technetium-99m-ECD in the normal medial temporal lobe. Oku, N., Matsumoto, M., Hashikawa, K., Moriwaki, H., Ishida, M., Seike, Y., Terakawa, H., Watanabe, Y., Uehara, T., Nishimura, T. J. Nucl. Med. (1997) [Pubmed]
  10. Carbohydrate-deficient transferrin and false-positive results for alcohol abuse in primary biliary cirrhosis: differential diagnosis by detection of mitochondrial autoantibodies. Bean, P., Sutphin, M.S., Liu, Y., Anton, R., Reynolds, T.B., Shoenfeld, Y., Peter, J.B. Clin. Chem. (1995) [Pubmed]
  11. A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Aubin, I., Adams, C.P., Opsahl, S., Septier, D., Bishop, C.E., Auge, N., Salvayre, R., Negre-Salvayre, A., Goldberg, M., Guénet, J.L., Poirier, C. Nat. Genet. (2005) [Pubmed]
  12. A Ca(2+) switch aligns the active site of calpain. Moldoveanu, T., Hosfield, C.M., Lim, D., Elce, J.S., Jia, Z., Davies, P.L. Cell (2002) [Pubmed]
  13. Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Barbaux, S., Niaudet, P., Gubler, M.C., Grünfeld, J.P., Jaubert, F., Kuttenn, F., Fékété, C.N., Souleyreau-Therville, N., Thibaud, E., Fellous, M., McElreavey, K. Nat. Genet. (1997) [Pubmed]
  14. Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency. Bugge, T.H., Kombrinck, K.W., Flick, M.J., Daugherty, C.C., Danton, M.J., Degen, J.L. Cell (1996) [Pubmed]
  15. Induction of cell differentiation by human immunodeficiency virus 1 vpr. Levy, D.N., Fernandes, L.S., Williams, W.V., Weiner, D.B. Cell (1993) [Pubmed]
  16. Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats. Mastropaolo, J., Nadi, N.S., Ostrowski, N.L., Crawley, J.N. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  17. Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. Giusti, P., Lipartiti, M., Franceschini, D., Schiavo, N., Floreani, M., Manev, H. FASEB J. (1996) [Pubmed]
  18. VCP/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death, phenotypes relevant to neurodegeneration. Hirabayashi, M., Inoue, K., Tanaka, K., Nakadate, K., Ohsawa, Y., Kamei, Y., Popiel, A.H., Sinohara, A., Iwamatsu, A., Kimura, Y., Uchiyama, Y., Hori, S., Kakizuka, A. Cell Death Differ. (2001) [Pubmed]
  19. Identification of the major protein components in breast secretions from women with benign and malignant breast diseases. Sánchez, L.M., Vizoso, F., Díez-Itza, I., López-Otín, C. Cancer Res. (1992) [Pubmed]
  20. L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide synthases. Frey, C., Narayanan, K., McMillan, K., Spack, L., Gross, S.S., Masters, B.S., Griffith, O.W. J. Biol. Chem. (1994) [Pubmed]
  21. Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Chen, J., Somanath, P.R., Razorenova, O., Chen, W.S., Hay, N., Bornstein, P., Byzova, T.V. Nat. Med. (2005) [Pubmed]
  22. Caspase-8 deficiency in T cells leads to a lethal lymphoinfiltrative immune disorder. Salmena, L., Hakem, R. J. Exp. Med. (2005) [Pubmed]
  23. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Chang, Q., Khare, G., Dani, V., Nelson, S., Jaenisch, R. Neuron (2006) [Pubmed]
  24. Tissue plasminogen activator-mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury. Akassoglou, K., Kombrinck, K.W., Degen, J.L., Strickland, S. J. Cell Biol. (2000) [Pubmed]
  25. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Novelli, G., Muchir, A., Sangiuolo, F., Helbling-Leclerc, A., D'Apice, M.R., Massart, C., Capon, F., Sbraccia, P., Federici, M., Lauro, R., Tudisco, C., Pallotta, R., Scarano, G., Dallapiccola, B., Merlini, L., Bonne, G. Am. J. Hum. Genet. (2002) [Pubmed]
  26. Monocyte chemotactic protein 1 is a potent activator of human basophils. Bischoff, S.C., Krieger, M., Brunner, T., Dahinden, C.A. J. Exp. Med. (1992) [Pubmed]
  27. The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Seamans, J.K., Yang, C.R. Prog. Neurobiol. (2004) [Pubmed]
  28. Alms1-disrupted mice recapitulate human Alström syndrome. Collin, G.B., Cyr, E., Bronson, R., Marshall, J.D., Gifford, E.J., Hicks, W., Murray, S.A., Zheng, Q.Y., Smith, R.S., Nishina, P.M., Naggert, J.K. Hum. Mol. Genet. (2005) [Pubmed]
  29. Epitope mapping of human thyroglobulin. Heterogeneous recognition by thyroid pathologic sera. Henry, M., Malthièry, Y., Zanelli, E., Charvet, B. J. Immunol. (1990) [Pubmed]
  30. CC chemokine receptor 8 in the central nervous system is associated with phagocytic macrophages. Trebst, C., Staugaitis, S.M., Kivisäkk, P., Mahad, D., Cathcart, M.K., Tucky, B., Wei, T., Rani, M.R., Horuk, R., Aldape, K.D., Pardo, C.A., Lucchinetti, C.F., Lassmann, H., Ransohoff, R.M. Am. J. Pathol. (2003) [Pubmed]
  31. Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. McGeehan, G.M., Becherer, J.D., Bast, R.C., Boyer, C.M., Champion, B., Connolly, K.M., Conway, J.G., Furdon, P., Karp, S., Kidao, S. Nature (1994) [Pubmed]
  32. Leptin is an endogenous protective protein against the toxicity exerted by tumor necrosis factor. Takahashi, N., Waelput, W., Guisez, Y. J. Exp. Med. (1999) [Pubmed]
  33. Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade. Immke, D.C., McCleskey, E.W. Neuron (2003) [Pubmed]
  34. Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions. Dubois, B., Masure, S., Hurtenbach, U., Paemen, L., Heremans, H., van den Oord, J., Sciot, R., Meinhardt, T., Hämmerling, G., Opdenakker, G., Arnold, B. J. Clin. Invest. (1999) [Pubmed]
  35. Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway. Blackburn, M.R., Lee, C.G., Young, H.W., Zhu, Z., Chunn, J.L., Kang, M.J., Banerjee, S.K., Elias, J.A. J. Clin. Invest. (2003) [Pubmed]
  36. Formation of eosinophilic and monocytic intradermal inflammatory sites in the dog by injection of human RANTES but not human monocyte chemoattractant protein 1, human macrophage inflammatory protein 1 alpha, or human interleukin 8. Meurer, R., Van Riper, G., Feeney, W., Cunningham, P., Hora, D., Springer, M.S., MacIntyre, D.E., Rosen, H. J. Exp. Med. (1993) [Pubmed]
  37. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. Nagy, J.A., Vasile, E., Feng, D., Sundberg, C., Brown, L.F., Detmar, M.J., Lawitts, J.A., Benjamin, L., Tan, X., Manseau, E.J., Dvorak, A.M., Dvorak, H.F. J. Exp. Med. (2002) [Pubmed]
  38. The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1. Santoso, S., Sachs, U.J., Kroll, H., Linder, M., Ruf, A., Preissner, K.T., Chavakis, T. J. Exp. Med. (2002) [Pubmed]
  39. Absence of the prion protein homologue Doppel causes male sterility. Behrens, A., Genoud, N., Naumann, H., Rülicke, T., Janett, F., Heppner, F.L., Ledermann, B., Aguzzi, A. EMBO J. (2002) [Pubmed]
  40. The crystal structure of the proprotein processing proteinase furin explains its stringent specificity. Henrich, S., Cameron, A., Bourenkov, G.P., Kiefersauer, R., Huber, R., Lindberg, I., Bode, W., Than, M.E. Nat. Struct. Biol. (2003) [Pubmed]
  41. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Bard, F., Cannon, C., Barbour, R., Burke, R.L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Lieberburg, I., Motter, R., Nguyen, M., Soriano, F., Vasquez, N., Weiss, K., Welch, B., Seubert, P., Schenk, D., Yednock, T. Nat. Med. (2000) [Pubmed]
  42. Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase 1. Olson, L.E., Bedja, D., Alvey, S.J., Cardounel, A.J., Gabrielson, K.L., Reeves, R.H. Cancer Res. (2003) [Pubmed]
  43. A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse. Shen, H.H., Ochkur, S.I., McGarry, M.P., Crosby, J.R., Hines, E.M., Borchers, M.T., Wang, H., Biechelle, T.L., O'Neill, K.R., Ansay, T.L., Colbert, D.C., Cormier, S.A., Justice, J.P., Lee, N.A., Lee, J.J. J. Immunol. (2003) [Pubmed]
  44. Molecules mimicking Smad1 interacting with Hox stimulate bone formation. Liu, Z., Shi, W., Ji, X., Sun, C., Jee, W.S., Wu, Y., Mao, Z., Nagy, T.R., Li, Q., Cao, X. J. Biol. Chem. (2004) [Pubmed]
  45. Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer's patients. Terrisse, L., Poirier, J., Bertrand, P., Merched, A., Visvikis, S., Siest, G., Milne, R., Rassart, E. J. Neurochem. (1998) [Pubmed]
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