Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new lipophilic immunomodulator, disaccharide tripeptide glycerol dipalmitoyl (DTP-GDP), has been synthesized and evaluated for its immunologic activity and toxicology. DTP-GDP alone or in liposomes is more effective as an adjuvant and in activating macrophages compared with muramyldipeptide (MDP). Preclinical studies demonstrate no evidence of toxicity, including vasculitis. DTP-GDP in liposomes has shown antitumor activity in phase I clinical trials.
Mol Biother 1990 Mar
PMID:Immunologic and toxicologic study of disaccharide tripeptide glycerol dipalmitoyl: a new lipophilic immunomodulator. 218 94

The pathogenesis of monocrotaline-induced pulmonary hypertension is not clear. Progressive pulmonary arteritis leading to vascular sclerosis, narrowing of the lumina, and thrombosis is the suspected sequence. To investigate this, we examined the effect of isosorbide dinitrate (ISDN), prednisolone, indomethacin, and elastase in 100 SD male rats, 4 weeks after the injection of monocrotaline (MCT) by cardiac catheterization, right ventricle-to-left ventricle plus septum weight ratio (RV/LV + S), histology, and electron microscopy. ISDN, a vasodilator, reduced the elevation of right ventricular (RV) pressure, RV/LV + S, and also pulmonary vascular remodeling; the characteristic histological feature was dilatation of small pulmonary arteries. Both prednisolone and indomethacin reduced RV pressure, RV/LV + S, and pulmonary vasculitis. Elastase, a protease which controls the metabolism of elastin in the arterial wall, likewise reduced RV pressure, RV/LV + S, and pulmonary vascular remodeling, with a significant decrease in elastosis of the small pulmonary arteries histologically. We concluded that all of the pathological processes resulting from arteritis are important in the development of MCT-induced pulmonary hypertension. In all experimental groups, decreased histopathologic changes correlated with decrease in the pressure. Elastase, which reduces pulmonary arterial sclerosis, is suggested as a new agent to treat pulmonary hypertension.
Exp Mol Pathol 1989 Jun
PMID:Comparative effects of isosorbide dinitrate, prednisolone, indomethacin, and elastase on the development of monocrotaline-induced pulmonary hypertension. 249 22

The generation of free oxygen radicals is believed to play an important pathogenic role in the development of various disorders. More than other tissues, the skin is exposed to numerous environmental chemical and physical agents such as ultraviolet light causing oxidative stress. In the skin this results in several short- and long-term adverse effects such as erythema, edema, skin thickening, wrinkling, and an increased incidence of skin cancer or precursor lesions. However, accelerated cutaneous aging under the influence of ultraviolet light, usually termed photoaging, is only one of the harmful effects of continual oxygen radical production in the skin. Others include cutaneous inflammation, autoimmunological processes, keratinization disturbances, and vasculitis. Vitamin E is the major naturally occurring lipid-soluble non-enzymatic antioxidant protecting skin from the adverse effects of oxidative stress including photoaging. Its chemistry and its physiological function as a major antioxidative and anti-inflammatory agent, in particular with respect to its photoprotective, antiphotoaging properties, are described by summarizing animal studies, in vivo tests on human skin and biochemical in vitro investigations. The possible therapeutic use in different cutaneous disorders, and pharmacological and toxicological aspects are discussed. Many studies document that vitamin E occupies a central position as a highly efficient antioxidant, thereby providing possibilities to decrease the frequency and severity of pathological events in the skin. For this purpose increased efforts in developing appropriate systemic and local pharmacological preparations of vitamin E are required.
J Mol Med (Berl) 1995 Jan
PMID:The role of vitamin E in normal and damaged skin. 763 44

The single-cell gel (SCG) test was used to study the induction and persistence of DNA damage by cyclophosphamide (CP) in human blood cells after treatment in vitro and in vivo. S9-mix-activated CP (from 0.1 mM upward) induced DNA effects in a concentration-dependent manner in the in-vitro SCG test. Blood cells from various donors showed considerable intra- and interindividual variability. Incubation of CP-treated blood samples at 37 degrees C caused a rapid decrease in DNA effects, but DNA migration was still significantly increased 1 hr after the end of the CP treatment. Comparative studies with the in vitro sister chromatid exchange (SCE) test were performed that demonstrated that much lower CP concentrations (about 100 times) were required for a significant induction of SCEs. A group of 11 patients who suffered from vasculitis/collagen disease and were treated with low CP doses (50-200 mg/day) exhibited an elevated level of DNA damage in the SCG test with peripheral blood cells, compared with a group of 11 control persons or 5 patients without chemotherapy. Increases in DNA damage were variable and not clearly related to the CP dose. SCE tests could successfully be performed with 5 out of the 11 CP-treated patients; all showed significantly increased SCE frequencies. For six patients no result could be obtained with the SCE test due to a failure of lymphocyte proliferation. Three multiple sclerosis patients who received high doses of CP were investigated with the SCG test before, during, and after the treatment. The results indicate that CP-induced DNA effects that are detectable with the SCG test persist in vivo for a period of several days, but for less than 2 weeks. The results of our study provide information with regard to the use of the SCG test in human monitoring. The advantages and limitations of the test are discussed.
Environ Mol Mutagen 1995
PMID:DNA-damaging effect of cyclophosphamide on human blood cells in vivo and in vitro studied with the single-cell gel test (comet assay). 773 35

Human parvovirus B19 is not only an acute self-limited infection causing erythema infectiosum, transient aplastic crisis, foetal hydrops and arthritis but can also be a chronic infection causing chronic anaemia and associated with chronic neuropathy and vasculitis. Serologic studies have proven to be the most sensitive way to detect acute infection in the immunologically normal patient while polymerase chain reaction (PCR) assays for B19 DNA are the most sensitive way to detect chronic infection. The ability to detect B19 in clinical specimens can be further increased with a second amplification step using nested primers. However, nested PCR is both time consuming and enhances the risk of false-positive results due to contaminating DNA. In this study, we developed a sensitive immunochemiluminescent Southern blot assay for detecting PCR amplified B19 DNA with a digoxigenin labelled primer. The sensitivity and specificity of this assay were comparable to nested PCR and at least 100-fold more sensitive than a single PCR amplification.
Mol Cell Probes 1994 Jun
PMID:Immunochemiluminescent Southern blot assay for polymerase chain reaction detection of human parvovirus B19 DNA. 796 92

Use of the immunosuppressant drug cyclosporine A (CSA) has resulted in improved renal graft survival. However, an increased incidence of arterial and venous thrombotic diseases, hemolytic-uremic type syndrome, and findings resembling vasculitis in the kidneys of patients with CSA nephrotoxicity and accelerated atherogenesis have been reported. These disorders may be related to CSA-induced abnormalities in platelet function. We report here that CSA causes increased ADP-stimulated aggregation in isolated platelet suspensions indicating that CSA has a direct effect on platelet function, independent of CSA interactions with plasma factors. Maximal hyperaggregability of ADP-stimulated platelets occurred following a 1 h preincubation period with CSA. Hyperaggregability of platelets due to the presence of CSA was dose-dependent and approached plateau between 200-500 ng/ml CSA. We determined that CSA exerted its effects through a signal transduction pathway involving the phosphorylation of two intracellular proteins, a 40 kD substrate of PKC (p47) and the 20 kD light chain of myosin (p20), a substrate of calcium/calmodulin dependent kinase. Preincubation with CSA resulted in a 200% increase in the phosphorylation of these proteins in platelets stimulated with ADP. We conclude that CSA enhances ADP-induced platelet aggregation and secretion, in part, by potentiating the phosphorylative response of specific intracellular proteins to stimulation by agonists. This process may be responsible for the increased thrombosis and atherogenesis observed in CSA-treated patients.
Cell Mol Biol Res 1993
PMID:Cyclosporine A enhances agonist-induced aggregation of human platelets by stimulating protein phosphorylation. 829 40

We have earlier reported that patients suffering from acquired immuno-deficiency syndrome (AIDS), systemic lupus erythematosus (SLE) with vasculitis, Wegner granulomatosis and certain types of late stage cancer have interferon inhibitory activity in their serum. The purpose of this study was to identify the factor(s) involved in this interferon inhibitory activity. Twenty patients with advanced AIDS, twenty patients with SLE and vasculitis and twenty normal healthy controls between ages 25-40 years were studied. In contrast to normal, healthy controls, significant interferon inhibitory activity was found in AIDS and SLE patients. This appears to be largely due to: (a) increased soluble circulating interferon alpha/beta receptors, (b) increased prostaglandin E2 levels which inhibits interferon and (c) a interferon inhibitory protein. Further understaging of the nature of interferon inhibitory activity in the patient's sera and development of anti-interferon inhibitory agents would greatly enhance interferons potential as a treatment modality.
Res Commun Mol Pathol Pharmacol 1997 Jun
PMID:Mechanism(S) of interferon inhibitory activity in blood from patients with AIDS and patients with lupus erythematosus with vasculitis. 926 85

Computer retrieval in a database, comprising 7,225 muscle cases, revealed that mitochondrial myopathies do not occur more frequently in inflammatory myopathies (3.74%) than in the whole series (3.69%). A more detailed study of inclusion body myositis (IBM), however, showed that severe mitochondrial alterations were apparent in about twice as many IBM cases as expected. This confirms recent studies of others although a causal relationship has thus far not been established. Identification of mitochondrial deletions by Southern blotting corresponded to the presence of severe structural abnormalities of mitochondria. Peripheral neuropathy of variable severity was noted in all cases of IBM and mitochondrial myopathy. By contrast, the association of severe mitochondrial abnormalities with polymyositis, systemic scleroderma, and vasculitis observed in some cases of the present series may be incidental or age dependent.
Mol Cell Biochem 1997 Sep
PMID:Mitochondrial abnormalities and peripheral neuropathy in inflammatory myopathy, especially inclusion body myositis. 930

The endothelin peptide family consists of the 21 amino acid isoforms endothelin-1, endothelin-2, endothelin-3, and sarafotoxin (a snake venom). Endothelin-1 has been isolated from the supernatant of endothelial cells and has subsequently been shown to be the most potent vasoconstrictor known to date and to be positively inotropic. This review summarizes some of the current literature pertaining to circulatory and myocardial effects of endothelins. Exogenously administered endothelin-1 has been demonstrated to increase peripheral resistance and blood pressure in a dose-dependent manner. However, during the first minutes of intravenous administration endothelins also decrease peripheral resistance and blood pressure, presumably due to the release of vasodilatory compounds such as nitric oxide, prostacyclin, and atrial natriuretic peptide. Endothelins appear to be involved in the pathogenesis of salt-dependent and renovascular animal models of experimental hypertension. Although endothelins appear to contribute to basal vascular tone, the role of endothelins in the pathophysiology of human hypertension remains unclear. In addition, a role has been suggested for endothelins in specific vascular lesions and inflammatory conditions (e.g., restenosis after coronary angioplasty, atherosclerotic coronary lesions, acute myocardial infarction, and vasculitis, glomerulonephritis). Endothelins are positively inotropic peptides in cardiac myocyte and papillary muscle preparations. They have also been demonstrated to induce hypertrophy of cardiac myocyte and may play an important role in ventricular processes that lead to chronic cardiac failure. The pathophysiological relevance of the endothelin system in human disease states is elucidated using selective (ET[A]) and nonselective (ET[A/B]) inhibitors of the endothelin receptors.
J Mol Med (Berl)
PMID:Circulatory and myocardial effects of endothelin. 942 21

Autoantibodies to MPO are associated with various forms of systemic vasculitis, including the renal limited form described as idiopathic crescentic glomerulonephritis. In vitro the antibodies are able to further activate primed neutrophils to the production of reactive oxygen species and the release of lysosomal enzymes. In vivo experimental studies in which an autoimmune response to MPO was induced in rats have demonstrated the in vivo potential of the autoantibodies to aggravate subclinical inflammatory lesions. In the right context, vasculitis and glomerulonephritis can ensue. Further studies are being directed to the precise characterization of autoimmune responses in order to obtain clues for the etiopathogenesis of the associated diseases.
J Mol Med (Berl) 1998 Sep
PMID:Autoantibodies to myeloperoxidase: clinical and pathophysiological significance. 976 46


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