Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses recent developments in infectious tubulointerstitial nephritis, including bacterial virulence factors, the interaction between leukocytes and bacteria, and early events in inflammation. In the area of vasculitis, little-studied specificities of antineutrophil cytoplasmic antibodies (ANCAs), including lactoferrin and elastase, plus newly described ANCAs with alpha-enolase specificity are discussed, along with newer studies on the pathogenesis of ANCA-mediated damage and animal models for ANCA-related vasculitis.
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PMID:Tubulointerstitial nephritis and vasculitis. 792 64

Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with clinically proven vasculitis have been described as reacting with proteins present in the granules of human neutrophils. We have studied sera from 59 ANCA positive patients to further characterize the antibody response. In addition to the antigens previously identified in the vasculitic syndromes (myeloperoxidase and serine proteinase 3) the majority of these sera contained antibodies that reacted with a cytosolic extract of neutrophils on Western blots. Nearly 40% of these sera had antibodies directed against a cytosolic protein(s) of molecular mass 48 kD. This protein was purified from neutrophil cytosol by ammonium sulphate fractionation, anion exchange and reverse phase chromatography. Amino acid sequence analysis of a proteolytic fragment of this protein identified it as alpha enolase. The anti-enolase antibodies only recognized the alpha isoform and were present in sera giving either a pANCA or cANCA staining pattern by indirect immunofluorescence. Antibodies to alpha enolase were also found in sera from patients with systemic lupus erythematosus, particularly those with renal disease. We conclude that the antibody response in ANCA positive vasculitis is not restricted to neutrophil granule proteins.
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PMID:Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. 845 67

Changes of the affective and cognitive function are usually associated with thyroid gland dysfunction. In autoimmune thyroid disease, these changes can be caused by thyroid dysfunction (hypo- or hyperthyroidism) or associated with the presence of antithyroid antibodies. Even a small change in thyroid hormone concentration is associated with change of cognitive function. In euthyroid older males, variation of total and free thyroxin accounts for about 10% of Wechsler adult intelligence test variance. In euthyroid females, lower cognitive function, measured by Mini Mental test, also correlates with blood thyroxin. Short-term (4 weeks) hypothyroidism induces clinically significant cognitivedysfunction, which is reversible by thyroid hormone substitution. Mild hypothyroidism (TSH less than 10) also induces reversible cognitive dysfunction. In hypothyroidism, PET scanning shows global reduction of brain blood flow and glucose metabolism. Hashimoto's encephalopathy is characterized by corticosteroid reversible encephalopathy associated with the presence of antithyroid antibodies. Encephalopathy can be manifested as multiple stroke-like episodes (vasculitis like), or as diffuse, progressive type characterized by dementia and psychiatric symptoms. In euthyroid patients with Hashimoto's thyroiditis and no evidence of neurological disease, SPECT showed brain perfusion abnormalities. Post mortem and brain biopsy findings can be normal or show perivascular lymphocytic infiltration. Recently, presence of antineuronal antibodies has been found in patients with Hashimoto's thyroiditis. Specific high reactivity against human alpha-enolase was high in patients with Hashimoto's encephalopathy, but absent in patients with other neurological disorders and healthy subjects. Specific antineural antibodies were found in another group of Hashimoto's encephalopathy patients. Furthermore, Ferracci et al, found antithyroid antibodies in the CSF of patients with Hashimoto's encephalopathy.
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PMID:[Autoimmune thyroid disease and brain]. 1640 64

The versatile clinical manifestations of the Hashimoto's chronic autoimmune thyroiditis often include psycho-neurological disorders. Although hypothyroidism disturbs significantly the ontogenesis and functions of central nervous system, causing in severe cases of myxedema profound impairment of cognitive abilities and even psychosis, the behavioral, motor and other psychoneurological disorders accompany euthyroid and slightly hypothyroid cases and periods of Hashimoto's disease as well, thus constituting the picture of so called "Hashimoto's encephalopathy". The entity, although discussed and explored for more than 50 years since its initial descriptions, remains an enigma of thyroidology and psychiatry, because its etiology and pathogenesis are obscure. The paper describes the development of current views on the role of thyroid in ontogeny and functions of brain, as well as classical and newest ideas on the etiology and pathogenesis of Hashimot's encephalopathy. The synopsis of the world case reports and research literature on this disorder is added with authors' own results obtained by study of 17 cases of Hashimoto's thyroiditis with schizophrenia-like clinical manifestations. The relation of the disease to adjuvant-like etiological factors is discussed. Three major mechanistic concepts of Hashimoto's encephalopathy are detailed, namely cerebral vasculitis theory, hormone dysregulation theory and concept, explaining the disease via direct action of the autoantibodies against various thyroid (thyroperoxidase, thyroglobulin, and TSH-receptor) and several extrathyroid antigens (alpha-enolase and other enzymes, gangliosides and MOG-protein, onconeuronal antigens) - all of them expressed in the brain. The article demonstrates that all above mentioned concepts intermingle and prone to unification, suggesting the unified scheme of pathogenesis for the Hashimoto's encephalopathy. The clinical manifestations, criteria, forms, course, treatment and prognosis of Hashimoto's encephalopathy and its comorbidity to other diseases - are also discussed in brief. The relation between Hashimoto's encephalopathy and non-vasculitis autoimmune encephalomyelitides of paraneoplastic and non-paraneoplastic origin is emphasized [1 figure, bibliography - 200 references].
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PMID:Thyroid gland and brain: Enigma of Hashimoto's encephalopathy. 3180 87