Lung cancer associated with pulmonary bulla. case report and review of literature.
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A few reports have suggested the possible association between lung cancer and bullous disease. We report a surgical case of lung adenocarcinoma located in close proximity to pulmonary bullae. A 48-year-old nonsmoker, asymptomatic male was found to have a pulmonary tumor mass and giant bulla in the right lung. Thoracotomy identified a tumor arising from a firm, scarred and contracted area close to the bulla wall. Based on this report and review of other cases in the literature, we emphasize the need for physicians to be aware of the potential development of lung cancer in patients with pulmonary bulla. (+info)
Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors.
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Toxic epidermal necrolysis (TEN) is a rare life-threatening adverse drug reaction characterized by a massive destruction of the epidermis. Immunohistological studies of skin biopsies of TEN showed infiltrates of predominantly CD8+ T lymphocytes even though other authors reported a prominent involvement of cells of the monocyte-macrophage lineage. The aim of this study was to characterize phenotypically and functionally the cells present in the cutaneous blister fluid of four patients with TEN. We first determined that lymphocytes were predominant in blister fluid obtained early, while monocytes/macrophages later became the most important population. We then showed that this lymphocyte population, mainly CD3+CD8+, corresponded to a peculiar cell subset as they expressed cutaneous leucocyte antigen, killer inhibitory receptors KIR/KAR and failed to express CD28 molecule. Functionally, we determined that blister T lymphocytes had a cytotoxic T lymphocyte (CTL)- and NK-like cytotoxicity. The role of this cytotoxic lymphocyte population present at the site of lesions during TEN remains to be understood. (+info)
Human anti-laminin 5 autoantibodies induce subepidermal blisters in an experimental human skin graft model.
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Patients with one form of cicatricial pemphigoid have IgG antibasement membrane autoantibodies against laminin 5 (alpha3beta3gamma2). Although passive transfer of rabbit anti-laminin 5 IgG to neonatal mice has been shown to induce subepidermal blisters that mimic those in patients, it has not been possible to directly assess the pathogenic activity of human autoantibodies in this animal model because the latter do not bind murine skin. To address this question, a disease model in adult mice as well as SCID mice bearing human skin grafts was developed. Adult BALB/C mice challenged with rabbit anti-laminin 5 IgG developed, in a concentration-related fashion, erythema, erosions, and crusts surrounding injection sites, histologic evidence of noninflammatory, subepidermal blisters, and deposits of rabbit IgG and murine C3 in epidermal basement membranes. Anti-laminin 5 IgG also induced subepidermal blisters in: adult complement-, mast cell-, and immuno-deficient mice; adult BALB/C mice pretreated with dexamethasone; and human skin grafts on SCID mice. Alterations did not develop in matching controls challenged with identical amounts of purified normal rabbit IgG or bovine serum albumin. Using this adult mouse model, human skin grafts on SCID mice were challenged with purified IgG from patients with alpha subunit-specific, anti-laminin 5 autoantibodies, or normal controls. Patient (but not control) IgG induced epidermal fragility as well as noninflammatory, subepidermal blisters in grafted human (but not adjacent murine) skin. Moreover, whereas all mice that received patient autoantibodies had anti-laminin 5 IgG in their circulation, deposits of human IgG were present only in the epidermal basement membranes of grafts. Interestingly, these in situ and circulating autoantibodies were predominately of the IgG4 subclass. These studies demonstrate that human anti-laminin 5 autoantibodies are pathogenic in vivo and describe an animal model that can be used to define disease pathomechanisms and biologically important domains within this autoantigen. (+info)
Integrin alpha(2)beta(1) (VLA-2) is a principal receptor used by neutrophils for locomotion in extravascular tissue.
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Cell adhesion molecules are critically involved in the multistep process of leukocyte recruitment in inflammation. The specific receptors used by polymorphonuclear leukocytes (PMN) for locomotion in extravascular tissue have as yet not been identified. By means of immunofluorescence flow cytometry and laser scanning confocal microscopy, this study demonstrated that surface expression of the alpha(2)beta(1) (VLA-2) integrin, though absent on blood PMN, is induced in extravasated PMN collected from human skin blister chambers, and rat PMN accumulated in the peritoneal cavity after chemotactic stimulation. Intravital time-lapse videomicroscopy was used to investigate chemoattractant-induced PMN locomotion in the rat mesentery in vivo. Local administration of function-blocking monoclonal antibody or peptide recognizing the alpha(2)beta(1) integrin reduced PMN migration velocity in the extravascular tissue by 73% +/- 3% and 70% +/- 10%, respectively (means +/- SD). The distance f-met-leu-phe peptide (fMLP)-stimulated human PMN migrated in a collagen gel in vitro was markedly reduced by treatment with anti-alpha(2) mAbs or peptide, whereas no effect was observed with antibodies or peptides recognizing the alpha(4)beta(1) or alpha(5)beta(1) integrins. Further evidence for a critical role of expression of alpha(2)beta(1) integrin in PMN locomotion in extravascular tissue was obtained in the mouse air pouch model of acute inflammation where chemoattractant-induced PMN recruitment was substantially inhibited by local anti-alpha(2) mAb treatment. Thus, expression of alpha(2)beta(1) integrin on extravasated PMN has been identified and a novel role of this receptor in regulating the extravascular phase of leukocyte trafficking in inflammation has been formulated. (Blood. 2000;95:1804-1809) (+info)
Large lung bullae in marijuana smokers.
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The case histories are presented of four men with multiple large upper zone lung bullae but otherwise relatively preserved lung parenchyma. Each had a history of significant exposure to marijuana. In three of the four cases the tobacco smoking load had been relatively small, suggesting a possible causal role for marijuana in the pathogenesis of this unusual pattern of bullous emphysema. (+info)
Pharmacokinetics and pharmacodynamics of levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in human skin blister fluid.
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The pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin. In addition, ex vivo bactericidal activity of SBF against Streptococcus pneumoniae and Staphylococcus aureus was studied. SBF containing levofloxacin and granulocytes killed 5.2 log of Streptococcus pneumoniae bacteria and 2.0 log of Staphylococcus aureus bacteria during a 6-h incubation. (+info)
Impaired monocyte CD11b expression in interstitial inflammation in hemodialysis patients.
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BACKGROUND: It is not known to what extent intravascular phenotypic alterations in adhesion molecule expression induced by hemodialysis influence the recruitment of monocytes and their ability to up-regulate CD11b at the local site of inflammation in the interstitium. Using a skin suction chamber technique, we addressed these issues in eight hemodialysis patients and in eight healthy subjects. METHODS: Two skin blisters were raised on the forearm of each individual and blister exudate collected. The blisters were then stimulated with autologous serum (active blister, intense inflammation) or buffer (control blister, intermediate inflammation), respectively. Thereafter the patients were treated with Cuprophan hemodialysis for four hours. After 10 hours, the exudate was aspirated from each chamber in all subjects. Monocyte count and expression of CD11b were analyzed in serum and blister fluid by flow cytometry. Then, monocytes from healthy blood donors were incubated in blister fluid from patients and healthy subjects in order to determine the local chemotactic activity in terms of CD11b up-regulation. Monocyte chemotactic protein-1 (MCP-1), a marker of systemic monocyte chemotactic activity, was also analyzed in serum at 0 and 10 hours in all individuals. RESULTS: The number of monocytes at the site of inflammation in the interstitium in hemodialysis patients correlated with the expression of CD11b on transmigrated cells (r = 0.78, P < 0.001). Monocytes collected in the active blister fluid of dialysis patients expressed equal levels of CD11b as cells collected from healthy subjects. By contrast, monocytes collected from the control blisters of patients expressed lower levels of CD11b than cells from healthy subjects (P < 0.01), despite equal interstitial biological activity of CD11b-mobilizing factors in blister fluid from patients and healthy subjects and the fact that patients had higher systemic chemotactic activity in terms of MCP-1 concentration in serum (P < 0.001). CONCLUSION: Monocytes from hemodialysis patients have the capacity to mobilize CD11b to the same extent as cells from healthy individuals at the inflammatory spot, but more intense stimuli are required for such actions, probably because of a transient refractoriness. (+info)
The alpha 5 chain of type IV collagen is the target of IgG autoantibodies in a novel autoimmune disease with subepidermal blisters and renal insufficiency.
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We describe a novel autoimmune disease characterized by severe subepidermal bullous eruptions and renal insufficiency with IgG autoantibodies directed against the NC1 domain of the alpha5(IV) collagen chain. In vivo deposits of IgG and C3 were found along the dermal-epidermal junction of skin lesions. The identity of the target antigen was determined by immunochemical analyses of candidate antigens using the patients' autoantibodies. The patients' IgG autoantibodies reacted with a 185-kDa polypeptide that was distinguished from the known autoantigens of the extracellular matrix including type XVII collagen, type VII collagen, or the alpha3, beta3, and gamma2 chains of laminin 5. Preincubation of the serum with recombinant alpha5(IV)NC1 domain of type IV collagen abolished immunoreactivity with the 185-kDa antigen. The serum reacted specifically with the alpha5(IV)NC1, among the six NC1 domains of type IV collagen, by Western blot and enzyme-linked immunosorbent assay analyses. The patients' autoantibodies reacted with normal skin and renal glomerulus but not with skin and glomerulus of a patient with Alport syndrome in which the basement membranes are devoid of the alpha5(IV) collagen chain. This study provided for the first time unambiguous evidence for the alpha5(IV) collagen chain as the target antigen in a novel autoimmune disease characterized by skin and renal involvement. (+info)