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Query: KEGG:D01398 (Dermatol)
 262,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non-specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell-related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage-related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume "psoriatic" phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA-DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)
J Dermatol 1992 Nov
PMID:Skin-infiltrating lymphocytes in normal and disordered skin: activation signals and functional roles in psoriasis and mycosis fungoides-type cutaneous T cell lymphoma. 129 60

Since alterations of epidermal Langerhans cells (LC) have been observed in humans infected with HIV, we investigated the morphology and function of these cells in murine acquired immunodeficiency syndrome (MAIDS), a murine model closely resembling human AIDS. The number as well as the shape of dendritic MHC class II+ cells from ear skin of C57BL/6 mice were similar in normal and infected animals. In mixed epidermal cell (EC) lymphocyte cultures, EC from infected mice and from normal mice stimulated allogeneic T cell proliferation to the same extent. In contrast to T cells from normal mice, however, T cells from infected mice did not respond to allogeneic spleen cells, confirming the presence of a T-cell defect in MAIDS. Subcutaneous injection of syngeneic mice with trinitrophenyl-modified MAIDS EC resulted in delayed ear swelling responses after challenge that were equivalent to those induced by hapten-modified EC from normal mice, suggesting that the contact sensitivity inducing potential of MAIDS LC was preserved. To investigate antigen presenting and processing function, EC and spleen cells were tested with the ovalbumin-specific IAb-restricted T cell hybridoma BO.17.10 and either ovalbumin 323-339 peptide or intact ovalbumin protein. MAIDS spleen cells had a reduced antigen presenting capacity compared with normal spleen cells, whereas EC from these mice showed the same processing and presenting capacity as normal controls. In summary, our results demonstrate that the frequency, morphology, level of MHC class II antigen expression and ability to process and present antigen is normal for LC from mice with MAIDS whereas the function of splenic T cells and APC from infected mice is significantly impaired.
Arch Dermatol Res 1992
PMID:Epidermal and splenic antigen-presenting cell function in a retrovirally induced murine immunodeficiency syndrome (MAIDS). 132 74

Purpura fulminans is a rare disease characterized by purpura ecchymosis, hypotension, and fever associated with disseminated intravascular coagulation. It often begins as a benign infectious process and subsequently progresses to a severe, catastrophic outcome. It is recognized to originate from congenital or acquired protein C deficiency. We present an unusual case of an adult with Xanthomonas maltophilia sepsis that subsequently developed into purpura fulminans with involvement of the four extremities. We discuss the importance of the protein C system in coagulation homeostasis and its relationship to purpura fulminans.
J Dermatol 1991 Apr
PMID:Purpura fulminans secondary to Xanthomonas maltophilia sepsis in an adult with aplastic anemia. 191 97

The seminal observation made 30 years ago that T cells do not discriminate between native and denatured proteins, whereas B cells generally do, can now be explained by the fact that T cells never see antigens in their native conformation and that intact proteins cannot associate simultaneously with MHC molecules and the TCR. This difference in the ability to recognize antigen based on conformational specificity appears to be a consequence of the fact that the T cell sees antigen not free in solution, but on the surface of an APC in association with MHC molecules. The metabolic events that protein antigens undergo within APC, prior to their presentation in an appropriately processed form to T cells, are called antigen processing. The end-product of antigen processing for CD4+ T cells is a relatively short peptide fragment bound to class II MHC molecules on the surface of an APC that can be recognized by the TCR on the T cells. Because this event is difficult to monitor directly, antigen processing can only be assayed in conjunction with the temporally distal event of T-cell activation, manifested ultimately as proliferative responses or lymphokine secretion. In addition to occupancy of the TCR by the peptide/class II complex, several other antigen-nonspecific receptor-ligand interactions between APC and T cells are required for optimal T-cell activation. M phi, B cells, and LC/DC comprise the principal APC for CD4+ T cells. M phi and B cells have been studied extensively with respect to their antigen processing and presenting capacities. Only recently, however, have such capacities been investigated in LC and DC; these studies now indicate freshly isolated LC (but not cultured LC and DC) to possess efficient antigen processing capabilities. In this respect, LC have been proposed to represent evolving (or "maturing") forms of DC: Freshly isolated LC (which retain morphologic and functional properties of epidermal LC in situ) are the equivalent of tissue forms of DC, whereas cultured LC resemble lymphoid or circulating DC. Cultured LC and DC appear to be the sole effective APC for inducing primary T-cell responses in vitro. Possibly underlying this property is the ability of cultured LC and DC (but not M phi, B cells, or freshly isolated LC) to induce formation of T-cell clusters during the course of such responses. The capacity of accessory cells to function as APC varies depending upon the type of APC and T cells examined.(ABSTRACT TRUNCATED AT 400 WORDS)
Dermatol Clin 1990 Oct
PMID:Antigen processing and presentation by epidermal Langerhans cells. Induction of immunity or unresponsiveness. 197 19

Lipodermatosclerosis of the lower extremity, with or without ulceration, is a common manifestation of severe venous disease and the result of sustained venous hypertension. The latter is generally a sequela of deep vein thrombosis. Factors that enhance clot formation or impair fibrinolysis contribute to the pathogenesis of venous disease. It is already established that faulty fibrinolysis may play a pathogenic role in patients with venous disease. We examined the possibility that patients with venous disease have abnormally low plasma levels of proteins C and S, two proteins whose deficiencies have been reported to cause an increased frequency of thromboembolic disease. Using immunologic and functional assays for plasma proteins C and S, we found that 4 (21%) of 19 patients with lipodermatosclerosis and leg ulcers had abnormally low levels of protein C or protein S. One of 7 patients with lipodermatosclerosis without ulceration had a profoundly depressed level of protein C and a history of cerebral stroke at a young age. Plasma levels of protein C were normal in five patients with arterial insufficiency severe enough to cause leg ulceration. We conclude that abnormally low plasma levels of proteins C and S may be found in patients with lipodermatosclerosis and venous ulceration. As with the abnormally low fibrinolytic activity in these patients, our findings indicate a possible propensity for increased thrombotic disease.
Arch Dermatol 1990 Sep
PMID:Protein C and protein S plasma levels in patients with lipodermatosclerosis and venous ulceration. 203 43

This review concentrates on those disorders in which superficial thrombophlebitis can be a significant or presenting clinical sign. Primary hypercoagulable states are those conditions associated with an increased risk of thrombosis caused by a specific measurable defect in the proteins of coagulation and/or fibrinolytic systems. These disorders are frequently inherited and include deficiencies of antithrombin III, heparin cofactor 2, protein C, protein S, abnormal fibrinolytic activity, dysfibrinogenemia, and Hageman trait. Patients with a lupus anticoagulant and anticardiolipin antibody syndrome with thrombotic episodes are also considered to have a primary hypercoagulable state. The physiology, pathophysiology, clinical characteristics, and treatment of primary hypercoagulable states are reviewed.
J Am Acad Dermatol 1990 Jun
PMID:Superficial thrombophlebitis. I. Primary hypercoagulable states. 219 91

Protein C (PC), a 62,000-molecular weight vitamin K-dependent serine protease zymogen, is a natural anticoagulant that occurs in plasma at 4 mg/L. Activated PC inactivates clotting factors V and VIII and is also profibrinolytic. Activated PC is enhanced in its anticoagulant activity by protein S (PS), another vitamin K-dependent protein. Protein S is found in platelets and endothelial cells as well as in plasma. Inherited PC deficiency and PS deficiency have been associated with venous thrombosis. Both heterozygous PC and PS deficiency appear to be inherited in an autosomal dominant manner in some families. Homozygous PC deficiency presents as neonatal purpura fulminans and results in massive venous thrombosis of the skin and other organs within the first few days of life. Symptomatic heterozygous PC deficiency and PS deficiency have been treated with oral anticoagulants, successfully minimizing recurrence of thrombosis. Coumarin-induced skin necrosis, a rare complication of oral anticoagulant therapy usually seen within three to five days of initiation of therapy, has also been associated with heterozygous PC deficiency. The short half-life of PC (six to eight hours) compared with most of the vitamin K-dependent clotting factors (greater than 30 hours) is the probable reason for this paradoxical response to oral anticoagulants in some PC-deficient patients, since a transient imbalance of procoagulant and anticoagulant factors may exist during initiation of oral anticoagulant therapy. Acquired deficiency of the PC pathway occurs in disseminated intravascular coagulation and possibly other diseases such as those associated with a lupus anticoagulant.
Arch Dermatol 1987 Dec
PMID:Coumarin necrosis, neonatal purpura fulminans, and protein C deficiency. 296 8

Protein C, when activated, is a vitamin K-dependent serine protease that has anticoagulant and profibrinolytic activities. An increased risk of thrombotic disease is associated with deficiency of this enzyme. A neonate developing purpura fulminans with internal thrombotic complications and congenital absence of protein C is described. Family studies showed partial protein C deficiency in the subject's symptom-free parents and two of three siblings. Clinically and histopathologically similar lesions are also seen in two acquired conditions in which there is a thrombotic tendency: coumarin necrosis and purpura fulminans of childhood, both of which are probably the result of transient protein C deficiency. We conclude that purpura fulminans can represent a cutaneous marker of acquired or congenital protein C deficiency.
Arch Dermatol 1988 Sep
PMID:Purpura fulminans. A cutaneous manifestation of severe protein C deficiency. 229 46

Three patients with karyotype XYY who had presented with deep vein thrombosis and leg ulcers (plus pulmonary embolism in two of them) were investigated for: (1) androgens (plasma testosterone measurement, testosterone oestradiol binding globulin (TeBG) assay, GnRH 50 micrograms test), and (2) haemostasis by fibrinolysis tests (euglobulin lysis time and area, antigenic plasminogen activator assay before and after 10 min venostasis). Full evaluation of haemostasis failed to demonstrate the presence of circulating anticoagulant or of antithrombin III, protein C and protein S deficiencies. One patient had neither hormonal nor fibrinolytic abnormality. The other two patients shared some clinical features with male hypogonadism (gynoid morphotype in both, hypotrophy of the testes in one, gynaecomastia in the other). They also had hormonal disorders ("over-response" to the GnRH test in one case, elevated TeGB in the other case) and abnormalities of fibrinolysis (poor response to venostasis, high baseline level of plasminogen activator). Response to venostasis became normal after 3 months of treatment with percutaneous dihydrosterone 125 mg per day in the two patients with initially poor response. The mechanism of venous pathology in XYY subjects is discussed. A genetic defect not involving the fibrinolysis system is possible since fibrinolysis was normal in one patient; however, abnormal fibrinolysis may have been responsible for the venous pathology in the other 2 patients. The role played by abnormalities of fibrinolysis in the pathogenesis of deep vein thrombosis and leg ulcers is recalled, and the possible implication of these abnormalities in patients with XYY karyotype is emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)
Ann Dermatol Venereol 1987
PMID:[Post-phlebitic leg ulcers and XYY karyotype: fibrinolysis and androgenic function tests. Apropos of 3 cases]. 343 47

An elderly woman who had been receiving long-term oral anticoagulant therapy developed skin and subcutaneous fat necrosis on five repeated occasions of extreme hypocoagulability, associated with coinciding periods of congestive cardiac failure. In each episode, the skin necrosis developed within days after the prothrombin time (as determined with Thrombotest) exceeded 200 s (International Normalized Ratio greater than 5.4). Widespread thrombosis in the subcutaneous vasculature and interstitial bleeding, as observed in a skin biopsy specimen, were consistent with a diagnosis of coumarin necrosis. On two occasions, an acquired functional protein C deficiency was present. It is hypothesized that an imbalance between anticoagulant and procoagulant vitamin K-dependent factors contributed to the pathogenesis of coumarin-induced skin necrosis. This imbalance was related to repeated periods of congestive heart failure.
Arch Dermatol 1986 Dec
PMID:Recurrent coumarin-induced skin necrosis in a patient with an acquired functional protein C deficiency. 378 74


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