RESUMO
The serum levels of several cytokines were determined in 94 patients with Adamantiades-Behçet's disease (ABD), aged 36.1+/-11.0 years, during the active stage (n = 75) and the inactive stage (n = 19) of the disease. A group of 75 healthy individuals matched for age and sex served as controls. Cytokine levels were determined using commercially available ELISA kits. Of the 75 patients with active disease and 19 with inactive disease, 38 (51%) and 4 (21%), respectively, and 23 healthy controls (31%) were found to have detectable levels of interleukin 8 (IL-8) in their serum (P < 0.05). Also, increased IL-8 serum levels were found in patients with active disease (median 12 pg/ml, P = 0.010) compared to patients with inactive disease (< or = 10 pg/ml) and to healthy controls (< or = 10 pg/ml). In particular, patients with oral aphthous ulcers (n = 51, 34 pg/ml) and neurological features (n = 4, 71 pg/ml) exhibited increased IL-8 levels. In contrast, there was no correlation between disease activity and the serum levels of IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNF-alpha), soluble intercellular adhesion molecule-1 or basic fibroblast growth factor (bFGF). In a second set of experiments, the involvement of dermal microvascular endothelial cells in IL-8 secretion was investigated. Immortalized human dermal microvascular endothelial cells (HMEC-1 cells) were maintained for 4 h in vitro with serum from 18 ABD patients or with IL-1beta, a known stimulator of IL-8 synthesis, TNF-alpha or their combination at five- to tenfold higher concentrations than those found in the serum of ABD patients. Increased IL-8 secretion was found after incubation with ABD patients' serum (median 20 pg/ml), but IL-1beta, TNF-alpha and IL-1beta + TNF-alpha failed to induce IL-8 secretion by HMEC-1 cells (< or = 1-1.2 pg/ml) in biologically relevant concentrations. Our study showed increased IL-8 serum levels in ABD patients with active oral and neurological manifestations. Human microvascular endothelial cells may, at least partially, be responsible for the enhanced IL-8 secretion in the active stage of the disease.
Assuntos
Síndrome de Behçet/fisiopatologia , Interleucina-8/sangue , Doença Aguda , Adulto , Síndrome de Behçet/sangue , Sangue , Linhagem Celular , Doenças do Sistema Nervoso Central/fisiopatologia , Citocinas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/imunologia , Feminino , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Interleucina-8/análise , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Úlceras Orais/fisiopatologiaRESUMO
The expression of C-myc p62, bcl-2, p53, PCNA and EBV-encoded LMP-1 proteins was studied by immunohistochemistry on paraffin-embedded skin specimens from 14 patients with early stage (premycotic erythema and second stage plaques) mycosis fungoides (MF), 21 patients with advanced stage MF (third stage plaques and tumors), 3 patients with Sezary's syndrome (SS) and 3 patients with pleomorphic medium and large cell cutaneous T-cell lymphomas (PML-CTCL). All 41 cases were also screened for the presence of EBV by using RNA in situ hybridization with EBER 1/2 oligonucleotides. Increased expression of C-myc p62, p53 and PCNA proteins was found in PML-CTCL and advanced stages of MF as compared to early stages of MF. These results suggest a relationship between levels of C-myc p62, p53 and PCNA proteins and aggressiveness of the cutaneous T-cell lymphomas. Furthermore, C-myc p62 and bcl-2 proteins were found to be frequently coexpressed in the present series. In view of the background information from in vitro findings and animal models that cooperation of C-myc and bcl-2 is important for lymphomagenesis, our results suggest that coexpression of these oncogenes may be implicated in the pathogenesis and/or the progression of cutaneous T-cell lymphomas. Neither LMP-1 expression nor EBV EBER l/2 transcripts were detected in our series suggesting that EBV is not involved in the pathogenesis of cutaneous T-cell lymphomas.
Assuntos
Herpesvirus Humano 4/isolamento & purificação , Micose Fungoide/química , Micose Fungoide/virologia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/virologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Antígeno Nuclear de Célula em Proliferação/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteína Supressora de Tumor p53/biossínteseRESUMO
BACKGROUND: The finite element analysis (FEA) is a recently introduced method in biomechanics that permits modeling of complex structures considering them as an aggregate of small elements. Skin flaps are highly suggested to be amenable to the continuum mechanic laws that underly the development of FEA. OBJECTIVE: A combination of "large deformation analysis," based on FEA with the criteria for skin flap selection, was attempted. METHODS: Serial defects were experimentally created on piglet skin stripes, which were consequently covered through designing appropriate flaps. Skin samples were modeled after the development of a computer FEA program and they were scanned by incorporating their photographs. RESULTS AND CONCLUSION: On the graphic interfaces the flap movement, the closure of the defect, and the whole deformation were found to match with the skin stripe postincisional alterations. This work permits the prediction and offers planning guides for different skin reconstructions.
Assuntos
Modelos Teóricos , Pele/fisiopatologia , Retalhos Cirúrgicos , Animais , Fenômenos Biomecânicos , SuínosRESUMO
The state of polymerization of actin and the organization of actin filaments is widely believed to be related to cellular transformation. Since the intracellular monomer (G) and filamentous (F) actin content reflects the state of microfilament polymerization, we measured the G/total actin ratio in primary cultures of normal and malignant human keratinocytes. In normal keratinocytes the mean value of this ratio was 0.30 +/- 0.03 (mean +/- SE, n = 15), while in basal cell carcinoma (BCC) keratinocytes it was 0.49 +/- 0.03 (n = 8) and in squamous cell carcinoma keratinocytes (SCC) 0.5 +/- 0.07 (n = 4), indicating a 1.7-fold increase of the G/total actin ratio in malignant cells. These results imply that the proportion of polymerized actin is decreased markedly in malignant keratinocytes, suggesting alterations of microfilament structures which probably occur during the transformation process. This was supported by the morphological changes of microfilament structures as assessed by fluorescence microscopy. A different distribution of actin filaments in normal and malignant cells became evident; stress-fibres were converging in patches at several points in SCC cells, when compared to normal keratinocytes. Furthermore, incubation of normal and malignant keratinocytes with cytochalasin B indicated differences in the resistance of their microfilament networks. After 1 h exposure to 10(-6) and 10(-5) M cytochalasin B, microfilaments in normal cells appeared to be less affected than their counterparts in neoplastic cells. Even in a high excess of cytochalasin B (10(-4) M), normal keratinocytes preserved their shape, while both basal cell and SCC were totally disrupted.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Actinas/análise , Queratinócitos/metabolismo , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Células Cultivadas , Citocalasina B/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/ultraestrutura , Microscopia de Fluorescência , Pele/metabolismo , Neoplasias Cutâneas/metabolismo , Células Tumorais CultivadasRESUMO
We have examined various autoimmunity parameters in AIDS with special emphasis on the expression of pemphigus and bullous pemphigoid antibodies. Sera from healthy seropositive individuals without syphilis (CS-, n = 17), seropositive individuals with syphilis (cs+, n = 11), and patients with AIDS (n = 6) were studied and compared with normal controls (n = 30); autoimmunity parameters related to dermatology were evaluated. Indirect immunofluorescence (IIF) for pemphigus and pemphigoid antibodies, antinuclear antibodies (ANA), anti-DNA antibodies, antismooth muscle antibodies (ASMA) antimitochondrial antibodies (AMA), and antithyroid antibodies (ATA) was carried out and findings were graded with a cumulative index (CI) for each patient group. Pemphigus and bullous pemphigoid-like antibodies (IgG, PV + BP) were detected in 33% of the AIDS patients. Statistically increased CI (P less than 0.01) was found in the CS- group compared with the CS+ group and in the AIDS group compared with CS- (P less than 0.01).
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Autoimunidade , Síndrome da Imunodeficiência Adquirida/complicações , Autoanticorpos/imunologia , Imunofluorescência , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Penfigoide Bolhoso/imunologia , Pênfigo/imunologia , Sífilis/complicações , Sífilis/imunologiaRESUMO
BACKGROUND: Interleukin 8 (IL-8) has recently been under focused investigation because of its possible participation in the evolution of Adamantiades-Behçet's disease. OBJECTIVE: The reliability of IL-8 as a serological marker for the activity of the disease was investigated in a prospective consecutive trial of 34 cases. METHODS: The activity of the disease was clinically evaluated by the number of actively involved organ systems registered on the day of blood sampling and by the presence of oral aphthous ulcers. Serum IL-8 levels were compared to C-reactive protein (CRP) values and the erythrocyte sedimentation rate. RESULTS: An association of IL-8 levels with the activity of the disease was detected when compared with both the number of active clinical signs (p = 0.024) and the presence of oral aphthous ulcers (p = 0.002). In contrast, no association of CRP and sedimentation rate with the activity of the disease could be detected. A weak correlation of IL-8 levels with sedimentation rate values at 2 h was found (R = 0.37, p = 0.032). CONCLUSION: Our results confirm previous data concerning the significance of IL-8 and, in addition, they provide first evidence for the reliability of IL-8 as a serological marker for assessment of the activity of Adamantiades-Behçet's disease in the follow-up of clinical and therapeutic studies.
Assuntos
Síndrome de Behçet/patologia , Adulto , Síndrome de Behçet/sangue , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Feminino , Humanos , Interleucina-8/sangue , Masculino , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Photodynamic therapy with delta-aminolevulinic acid is a promising alternative treatment for superficial skin malignancies. OBJECTIVE: Further clinical experience, study of tissue alterations leading to recovery, and correlation/prediction of the therapeutic response through in vivo skin color changes as represented by erythema development. METHODS: The therapeutic procedure, sequential histology and histochemistry, and the development of a remote machine vision system to measure, map, and monitor the erythema development. RESULTS/CONCLUSIONS: A high cure response rate with adequate follow-up was shown. A significant correlation of the clinical-histologic response of tumors subjected to treatment with the erythema measurements implies that erythema inspection and quantitative analysis offer a reliable predictor of the therapeutic outcome and a clue for optimization of this treatment modality.