Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036421 (PSS)
 10,989 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Scleroderma is reviewed as a complex disease of vascular, connective-tissue, and inflammatory reactions. If the scleroderma syndromes related to occupational, immunologic, inflammatory, metabolic, and genetic factors are recognized, then true progressive systemic scleroderma (PSS) appears to be a disease of vascular fibrosis with secondary inflammatory phases. The primary pathology appears to be a fibromucinous change of the vascular endothelium. The vessels also demonstrate altered reactivity to cold and to serotonin. Biopsy of the skin of the inflammatory or mesenchymal scleroderma may reveal (by positive direct immunofluorescence) deposition of globulins at the basement membrane zone. Evaluation of scleroderma is discussed and a system of clinical staging of PSS is proposed which relates the organ involvement to the prognosis.
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PMID:Pathogenesis and staging of scleroderma. 5 29

Proper classification of patients into diffuse cutaneous and limited cutaneous subsets and the anticipation of complications are the keys to the management of subjects with systemic sclerosis (scleroderma). Patients with early diffuse disease and rapidly progressive skin thickening are at highest risk of developing serious disease of the internal organs (intestine, lung, heart, kidney) and should be considered for disease modifying treatment. The targets of the disease and sites of possible intervention are vascular endothelium (vasoprotective agents), mononuclear cell subsets (immunosuppressive agents), and fibroblasts (colchicine, D-penicillamine). A number of new agents with sound scientific rationale are currently undergoing therapeutic trials. Much can be done to improve the lifestyle of those with scleroderma. The most dramatic recent development is the ability to reverse kidney disease by the prompt use of angiotensin converting enzyme inhibitors and modern methods of renal dialysis and transplantation. Scleroderma is not a hopeless disease.
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PMID:Treatment of systemic sclerosis. 175 Aug 1

Proper classification of patients into diffuse cutaneous and limited cutaneous subsets and the anticipation of complications are the keys to the management of individuals with systemic sclerosis (scleroderma). Patients with early diffuse disease and rapidly progressive skin thickening are at highest risk to develop serious internal organ involvement (intestine, lung, heart, kidney) and should be considered for disease modifying therapy. The targets of the disease and sites of possible intervention are vascular endothelium (vasoprotection agents), mononuclear cell subsets (immunosuppressive agents), and fibroblasts (colchicine, D-penicillamine). A number of new therapeutic agents with sound scientific rationale are undergoing therapy trials. Much can be done to improve the lifestyle of the scleroderma sufferer. The most dramatic recent development is the ability to reverse kidney involvement with prompt use of angiotensin converting enzyme inhibitors and modern methods of renal dialysis and transplantation. Scleroderma is not a hopeless disease.
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PMID:Treatment of systemic sclerosis. 267 35

The immune response to connective tissue components of basement membrane (type IV collagen and laminin) and to interstitial collagen (type I) has been examined in human and murine systems. We also examined the role that immunologic sensitization to autologous connective tissue components might play in inducing an inflammatory response resulting in pathologic sequelae. Mice receiving a single subcutaneous injection of 5 micrograms type IV or type I murine collagens, or murine laminin in complete Freund's adjuvant mount a delayed-type hypersensitivity response characterized by a mononuclear cell infiltrate when challenged in the footpad with the sensitizing antigen. Cell-mediated immunity to these connective tissue antigens can be transferred to normal syngeneic mice with sensitized T-lymphocytes. In addition, repeated immunizations with these homologous connective tissue components elicit antibody responses in mice. Our data demonstrate the immunogenic nature of types IV and I collagen, and of laminin in a syngeneic murine model. We have demonstrated autoantibodies to the basement membrane and interstitial collagens in the sera of patients with scleroderma (systemic sclerosis); ELISA ratios correlate directly with the extent of pulmonary fibrosis in these patients. Anti-type IV collagen autoantibodies were found to be primarily IgM and anti-type I collagen antibodies, primarily IgG. An antibody response to autologous connective tissue antigens could lead to complement activation, immune complex formation, and deposition of the complexes along vascular endothelium with recruitment of blood monocytes in situ, mirroring the early scleroderma lesion (perivascular mononuclear cell filtrates). In vitro we examined the role of human peripheral blood mononuclear cells in the activation of fibroblasts. Adherent human blood monocytes release mediators which stimulate fibroblast proliferation and collagen deposition. A model is presented for the induction of immunity to autologous connective tissue components, leading to mononuclear cell inflammation, fibroblast activation and fibrosis. Selective immunity to basement membrane collagens may influence the clinical expression of diffuse connective tissue syndromes such as scleroderma (systemic sclerosis).
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PMID:Immune response to connective tissue components of the basement membrane. 621 63

Biological investigations are useful from three main view points in systemic scleroderma: diagnosis: the demonstration of antinuclear antibodies which are quite specific for these conditions: antinuclear anti-ECT (nRNP, Scl 70, KU, PM 1) and anticentromere antibodies; prognosis: the presence of some antibodies is associated with a more favourable outcome: anti-nRNP and Sharp's syndrome, anti-centromere and the CREST syndrome, anti-KU and syndromes overlapping with polymyositis; pathogenic: the study of abnormalities of T-lymphocyte function, immunogenetic (HLA grouping) studies, cytotoxic factors for vascular endothelium, mitogenic factors of fibroblasts and the "chromosome breaking" factor.
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PMID:[What can be expected of biological tests in scleroderma?]. 633 33

To study the functional reactivity of the cutaneous microcirculation in progressive systemic sclerosis (PSS), hyperemic responses after arterial occlusion (3 min) and during local heating (42 degrees C) were investigated with simultaneous measurements of red blood cell flux and cutaneous oxygen tension (pcuO2) of the skin in female patients (n = 19) with PSS and in healthy female controls (n = 15). Additionally, serum levels of 6-keto-prostaglandin 1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, were compared to the microcirculatory data, and both were used to evaluate further a standardized therapy with 10-d intravenous calcitonin (100 IU/d) infusion in six PSS patients. In PSS, the initial mean pcuO2 value was significantly reduced and was inversely proportional to flux and to PGF1 alpha levels, whereas the flux and pcuO2 responses to the above hyperemic stimuli showed significant reductions, revealing a pattern of "hyperemic hypoxia" probably due to exhausted functional reserves of cutaneous perfusion. During calcitonin infusion significant rises in pcuO2 and temporarily in PGF1 alpha and flux were found. After 10 d of therapy, increased pcuO2 was associated significantly with decreased flux, indicating a shifting of blood from deeper regulatory vessels to the subepidermal capillaries. Both clinical improvement and the results of microcirculatory measurements demonstrate a beneficial effect of calcitonin on the cutaneous microcirculation in PSS patients, possibly due in part to a short-term increase in release of endogenous prostacyclin from the vascular endothelium during the infusion. The disturbed reactivity of the dermal vessels in PSS is important for the evaluation of therapeutic concepts and stresses, together with the elevated PGF1 alpha plasma levels, vascular factors in the pathogenesis of PSS.
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PMID:Microcirculatory functions in systemic sclerosis: additional parameters for therapeutic concepts? 834 23

The Raynaud phenomenon occurs in 90-100% of patients with systemic scleroderma. It is caused by dysregulation of the vascular tone between vasoconstrictive and vasodilatory influences. Early damage to the vascular endothelium and the activation of platelets lead to the release of vasoactive substances. Structural and function impairment of the perivascular neural fibers contributes to the vasospasm. New vasodilatory treatment strategies, e.g. infusions with calcitonin gene-related peptides, could be useful in the control of vasospasm in the peripheral extremities as well as internal organs in systemic scleroderma.
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PMID:[Raynaud phenomenon and scleroderma]. 870 77

In systemic sclerosis, the exaggerated generalized vasospastic tendency is clinically represented by Raynaud's phenomenon as shown by an early digital arterial closure after cold stimulation, and by an inadequate vasodilatory response to heat. The phenomenon is not restricted to the extremities, and can also occur in internal organs. Repeated attacks of Raynaud's phenomenon may contribute to vascular disease in systemic sclerosis by a mechanism of reperfusion injury of the endothelium, and may contribute to tissue fibrosis. Although the aetiology and pathogenesis of Raynaud's phenomenon remain unknown, recent advances in the understanding of mechanisms of vascular tone control provide us with an opportunity to reconsider the pathogenetic process of Raynaud's phenomenon. It is now clear that neuropeptides, the vascular endothelium, and platelets are the three major contributors to the control of vascular tone. Our hypothesis suggests the presence of a sensory nervous system failure, leading to an unopposed endothelial and platelet control of vascular tone. Endothelial injury and platelet activation in systemic sclerosis lead to a shift in vascular function to a pro-vasospastic function not balanced by a vasodilatory sensory input; thus, enhanced vasospasm is generated. The investigation of the role of local vascular mediators in vasospasm may lead to a better understanding of vascular tone control and of Raynaud's phenomenon pathophysiology in systemic sclerosis.
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PMID:Raynaud's phenomenon and systemic sclerosis. 897 38

Membrane thrombomodulin (TM) is a very efficient natural anti-thrombin glycoprotein with anticoagulant properties expressed on endothelial cell surface. Circulating plasmatic thrombomodulin (TMp) detected by enzyme immunoassay in plasma is considered as a cell marker of endothelial injury. The TMp levels are increased in many conditions (diabetes mellitus, atheromatous disease...). In cases of collagen vascular diseases, where vascular endothelium damage is suspected, TMp is increased particularly in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). It is noteworthy that the TMp level is correlated with disease activity. Since TMp is a non specific marker of endothelial damage, it may be of interest as a useful marker for the supervision of these diseases. Further studies are needed on larger series. TMp level change during spontaneous evolution or under treatment will help determine wether TMp is a predictor and prognostic marker of these systemic diseases.
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PMID:[Assay of plasma thrombomodulin in systemic diseases]. 909 31

An hypothesis for the pathogenesis of systemic sclerosis is introduced. It posits a genetic background with environmental stimuli that activate immune cells. The immune cells, in turn, may damage vascular endothelium, cause proliferation of fibroblasts, or stimulate fibroblasts to produce collagen. Endothelial cell damage can also activate the immune system or induce fibroblast proliferation. Associated with fibroblast proliferation may be immune activation or collagen production. Finally, collagen production and end organ damage can induce immune activation thus perpetuating the cycle. Raynaud's phenomenon, an early finding in systemic sclerosis can cause vascular damage, thus entering the cycle at a different point than other environmental stimuli. This hypothesis will undoubtedly require change as data emerge, but it presents a conceptual model for testing and modification.
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PMID:Hypothesis for the pathogenesis of systemic sclerosis. 915 Jan 19


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