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)

Macrophages represent a critical component in the inflammatory lesions of giant cell arteritis. By combining immunohistochemistry and in situ hybridization, we have analyzed the functional heterogeneity of tissue-infiltrating macrophages in patients with untreated vasculitis. 20% of macrophages in temporal artery tissue synthesized IL-6-specific mRNA and produced IL-6 and IL-1 beta proteins. IL-6 and IL-1 beta production was not limited to CD68+ cells in the lymphoid aggregates but was a feature of CD68+ cells dispersed throughout the tissue. 50% of tissue-infiltrating CD68+ cells synthesized 72-kD type IV collagenase. Only a small subset of CD68+ cells produced cytokines as well as collagenase, indicating functional specialization or distinct differentiation stages of CD68+ cells in the inflamed tissue. Activation of CD68+ cells was not restricted to tissue-infiltrating cells. Expression of IL-6 and IL-1 beta was found in 60-80% of circulating monocytes of patients with untreated giant cell arteritis, whereas collagenase production was restricted to tissue macrophages. IL-6 and IL-1 beta production by the majority of circulating monocytes was a shared feature of patients with giant cell arteritis and polymyalgia rheumatica but was not found in rheumatoid arthritis. These data suggest that giant cell arteritis has two components of disease, an inflammatory reaction in vessel walls and a systemic activation of monocytes. Systemic monocyte activation can manifest independently without vasculitis as exemplified in patients with polymyalgia rheumatica.
 ...
PMID:Functional profile of tissue-infiltrating and circulating CD68+ cells in giant cell arteritis. Evidence for two components of the disease. 808 54

Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein that exerts a proliferative effect specifically on endothelial cells. VEGF can increase vascular permeability and collagenase activity, is chemotactic for monocytes, and may dilate blood vessels. It can be induced by phorbol ester and cAMP in both mesenchymal and epithelial cells. In vitro cell culture experiments suggest that VEGF is upregulated by oxygen deprivation. In this study we tested whether in vivo acute and/or chronic reduction of renal blood flow by vascular obstruction would result in increased expression of VEGF mRNA and protein. Three normal kidneys, five human kidneys with narrowing of preglomerular vessels by vascular rejection or by vasculitis, and eight kidneys with nephrosclerosis and/or diabetic nephropathy were examined. In situ hybridization with 35S-labelled riboprobes showed a pronounced expression of VEGF mRNA in acutely hypoxic proximal and distal tubules of both the cortex and medulla; VEGF protein was demonstrated in the epithelia of these tubules by immunohistochemistry. In kidneys with chronically reduced blood flow, the majority of atrophic tubules were negative for VEGF mRNA and protein, although interstitial cells expressed VEGF mRNA. In arcuate arteries showing intimal and adventitial fibrosis, some medial smooth muscle cells were positive for VEGF mRNA. In glomeruli with segmental sclerosis, viable podocytes showed a prominent signal for VEGF mRNA. Mesangial cells did not express VEGF in the cases studied. It is possible that hypoxia itself led to the upregulation of VEGF in tubular epithelia and vascular smooth muscle cells. The vasodilatory and permeability-promoting effects of the endothelial growth factor produced by damaged tubular epithelia may constitute a mechanism to alleviate a decrease in blood flow and substrate availability and to re-establish vascular integrity.
 ...
PMID:Expression of vascular endothelial growth factor in renal vascular disease and renal allografts. 855 88

End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFbeta1-expressing CD68+ cells coproduce IL-1beta and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFbeta1+ CD68+ cells places them in the vicinity of IFN-gamma secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFbeta and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFbeta1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFbeta1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.
 ...
PMID:Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis. 883 14

Two inflammatory vascular diseases often show multinucleated macrophages: Takayasu's disease and Horton's disease. Takayasu's disease is a segmentary panarteritis most prominent in the adventitia. Lesions show an inflammatory infiltrate close to the external elastic lamina. Progressive stenosis of the artery, sometimes complicated by calcifying atheroma is the typical course. Horton's disease or temporal arteritis is another segmentary arteritis. Lesions show a mixed inflammatory infiltrate partly localized in the adventitia where there are T CD4+ lymphocytes secreting II-2 and IFN-gamma and also macrophages expressing TGF beta 1, IL-6 and IL-1 beta, and partly situated in the interior part of the wall, around the internal elastic lamina, and mostly made of macrophages and giant cells which produce TNF, collagenase and nitric oxide that are responsible for destruction of the wall. The variety and subtleness of some lesions do not always make a precise diagnosis possible. But any inflammatory vascular lesion, even slight, can reveal a systemic vasculitis.
 ...
PMID:[Pathology of giant cell arteritis]. 992 94

Phenytoin (diphenylhydantoin or Dilantin) is a highly effective and widely prescribed anticonvulsant agent used in the treatment of grand mal and psychomotor epilepsy. In dermatology, phenytoin has been used to treat ulcers, epidermolysis bullosa, and inflammatory conditions. Its mechanism appears to involve its ability to inhibit collagenase. Its topical use for the promotion of wound healing seems promising but requires further trials. The side effects of phenytoin continue to create significant morbidity. Common side effects include gingival hyperplasia, coarsening of the facies, and hirsutism. Rarer cutaneous side effects include drug-induced lupus, purple-hand syndrome, pigmentary alterations, and IgA bullous dermatosis. It can cause generalized cutaneous eruptions that include a maculopapular exanthem, Stevens-Johnson syndrome, generalized exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, and fixed-drug eruptions. Phenytoin is linked to a hypersensitivity syndrome manifested by fever, rash, and lymphadenopathy. Patients receiving phenytoin may develop pseudolymphoma or, rarely, malignant lymphoma and mycosis-fungoides-like lesions. Phenytoin can effect clotting function. Phenytoin can alter vitamin and mineral levels. Prenatal exposure to phenytoin may result in a spectrum of structural, developmental, and behavioral changes known as the fetal hydantoin syndrome. After 60 years of use, phenytoin uses and mechanisms of action have yet to be fully defined; the drug remains a useful tool and an important subject for additional research.
 ...
PMID:Phenytoin in cutaneous medicine: its uses, mechanisms and side effects. 1295 53

The most frequent causes of leg ulcers include venous incompetency (superficial and deep), arterial insufficiency, trauma, vasculitis, and neoplasm. Leg ulcers from injury by stingrays are quite rare. In this case report, we describe a leg ulcer caused by a stingray sting complicated by infection, which healed completely without surgery. In addition, since there few cases in the literature describing such traumas, we performed a comprehensive review of the literature. Important is the fact that the wound healing was complete without resorting to surgery, but only with a correct targeted antibiotic therapy and the use of a collagenase, which has the particularity of having hyaluronic acid as a component.
...
PMID:Clinical Examination and Treatment of a Leg Ulcer Caused by a Stingray Puncture. 2487 61