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Biomedical subjects

M Gonçalo

Publications and source records attributed to M Gonçalo.

At least 19 recordsLinked to original sources
PubMed2005

Contact sensitizers downregulate the expression of the chemokine receptors CCR6 and CXCR4 in a skin dendritic cell line.

Chemokines are involved in the control of dendritic cell (DC) trafficking, which is critical for the immune response, namely in allergic contact dermatitis (ACD). In this work, we investigated by flow cytometry the effect of the contact sensitizers 2,4-dinitrofluorobenzene (DNFB), 1,4-phenylenediamine (PPD) and nickel sulfate (NiSO(4)), on the surface expression of the chemokine receptors CCR6 and CXCR4 in DC. As an experimental model of a DC we used a fetal skin-derived dendritic cell line (FSDC), which has morphological, phenotypical and functional characteristics of skin DC. Our results show that all the skin sensitizers studied decreased the membrane expression of the chemokine receptors CCR6 and CXCR4. In contrast, 2,4-dichloronitrobenzene (DCNB), the inactive analogue of DNFB without contact sensitizing properties, was without effect on the surface expression of these receptors. Lipopolysaccharide (LPS), which induces the maturation of DC, also reduced surface CCR6 and CXCR4 expression.

Animals↗
PubMed2005

Detection of axillary metastases in breast cancer patients using ultrasound and colour Doppler combined with fine needle aspiration cytology.

The aims of this study were to evaluate the diagnostic value of ultrasonography and colour Doppler combined with fine needle aspiration (FNA) cytology for the detection of non-palpable axillary lymph node metastases in breast cancer patients. Forty patients with operable breast cancer (T1/T2), invasive carcinoma, not submitted to neo-adjuvant therapy, underwent axillary ultrasonography and colour Doppler preoperatively. FNA cytology was performed on axillary lymph nodes presenting ultrasonographic and/or Doppler suspicious features. A total of 542 lymph nodes were surgically removed from the 40 patients; 19 were metastatic lymph nodes. Ultrasound-guided FNA detected metastases in six out of 11 histologically node-positive patients. Sensitivity and specificity in this preliminary study was 55% and 100%, respectively. These are the preliminary results of a prospective study that has the purpose of reducing the sentinel node procedures in breast cancer patients with clinically negative axillae, but positive FNA cytology.

Adult↗
PubMed2004

Photopatch testing: a consensus methodology for Europe.

A group of interested European Contact Dermatologists/Photobiologists met to produce a consensus statement on methodology, test materials and interpretation of photopatch testing. While it is recognized that a range of local variables operate throughout Europe, the underlying purpose of the work is to act as an essential preamble to a Pan European Photopatch Test Study focusing particularly on sunscreen chemicals.

Dermatitis, Photoallergic↗
PubMed2004

Diagnostic value of ultrasound and color Doppler in identifying axillary lymph node metastases in patients with breast cancer.

PURPOSE: The aim of this study was to evaluate the diagnostic ability of ultrasound and color Doppler in axillary lymph node metastases of patients with breast cancer. MATERIAL AND METHODS: A prospective study including 55 patients with primitive, invasive, node negative breast cancer who underwent preoperative axillary ultrasound and color Doppler. Doppler and morphologic ultrasound criteria were applied to the identification of axillary lymph node metastases. RESULTS: The imagery study of all 55 patients identified a total of 141 nodes; 44 were considered to be positive according to established criteria. The histological examination of the axillary dissection revealed a total of 989 nodes; 77 out of 989 presented metastases; all invaded nodes belonged to 21 patients. The previous imagiologic study was positive for axillary lymph node metastases in 15 out of these 21 patients. A sensitivity of 71.4%, a specificity of 71.4%, a negative predictive value of 80.6% and a positive predictive value of 60.0% were achieved. CONCLUSION: The imagery study of the axillary region through ultrasound and color Doppler might be useful in assessing axillary lymph node metastases in patients with breast cancer.

Breast Neoplasms↗
PubMed2001

LPS induction of I kappa B-alpha degradation and iNOS expression in a skin dendritic cell line is prevented by the janus kinase 2 inhibitor, Tyrphostin b42.

The Janus kinase (JAK) family of protein tyrosine kinases are activated in response to a wide variety of external stimuli. Here we have investigated whether the janus kinase 2 (JAK2) is involved in the induction of nitric oxide synthase type II (iNOS) expression in a mouse fetal skin dendritic cell line (FSDC). In FSDC the expression of iNOS protein and nitric oxide production, in response to the lipopolysaccharide (LPS) stimulus (5 microg/ml), is inhibited by the specific inhibitor of the JAK2, tyrphostin B42 with an half maximal inhibitory concentration (IC(50)) of 9.65 microM. The antioxidant compound pyrrolidinedithiocarbamate (PDTC) inhibits both the nitrite production with an IC(50) of 16.6 microM and the iNOS protein expression in FSDC. In addition, LPS induces the activation of NF-kappa B, and tyrphostin B42 prevents the degradation of the cytosolic factor I kappa B-alpha and blocks the translocation of the NF-kappa B p65 protein subunit into the nucleus. These results indicate that the JAK family of protein kinases and the transcription factor NF-kappa B are involved in the induction of iNOS protein expression in FSDC stimulated with LPS.

Animals↗
PubMed2001

Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions.

Skin testing with a suspected drug has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of positive drug skin tests are published, but without detailed information concerning the clinical features of the CADR and the method used in performing drug skin tests, such data are not very informative. A working party of the European Society of Contact Dermatitis (ESCD) for the study of skin testing in investigating cutaneous adverse drug reactions, has proposed the herein-reported guidelines for performing skin testing in CADR in order to standardize these procedures. In each reported case, the imputability of each drug taken at the onset of the CADR and a highly detailed description and characterization of the dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed according to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested diluted at 30% pet. (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq. In severe CADR, drug patch tests are performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR. Drug prick tests are performed on the volar forearm skin with the commercialized form of the drug, but with sequential dilutions in cases of urticaria. Intradermal tests (IDT) are performed with sterile sequential dilutions (10-4, 10-3, 10-2, 10-1) of a pure sterile or an injectable form of the suspected drug with a small volume of 0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4 for patch tests, at D1 for prick tests and IDT. All these tests also need to be read at 1 week. The success of skin tests varies with the drug tested, with a high % of positive results, for example, with betalactam antibiotics, pristinamycin, carbamazepine and tetrazepam on patch testing, or with betalactam antibiotics and heparins on delayed readings of IDT. The results of drug skin tests also depend on the clinical features of the CADR. The use of appropriate control patients is necessary to avoid false-positive results.

Drug Eruptions↗
PubMed2001

Granulocyte-macrophage colony-stimulating factor activates the transcription of nuclear factor kappa B and induces the expression of nitric oxide synthase in a skin dendritic cell line.

Nitric oxide (NO) produced by skin dendritic cells and keratinocytes plays an important role in skin physiology, growth and remodelling. Nitric oxide is also involved in skin inflammatory processes and in modulating antigen presentation (either enhancing or suppressing it). In this study, we found that GM-CSF stimulates the expression of the inducible isoform of nitric oxide synthase (iNOS) in a fetal-skin-derived dendritic cell line (FSDC) and, consequently, increases the nitrite production from 11.9 +/- 3.2 micromol/L (basal level) to 26.9 +/- 4.2 micromol/L. Pyrrolidinedithiocarbamate (PDTC) inhibits nitrite production, with a half maximal inhibitory concentration (IC50) of 19.3 micromol/L and the iNOS protein expression in FSDC. In addition, western blot assays revealed that exposure of FSDC to GM-CSF induces the phosphorylation and degradation of the inhibitor of NF-kappaB (IkB), with subsequent translocation of the p50, p52 and RelB subunits of the transcription nuclear factor kappa B (NF-kappaB) from the cytosol to the nucleus. Electrophoretic mobility shift assays (EMSA) showed that FSDC exposure to GM-CSF activates the transcription factor NF-kappaB. Together, these results show that GM-CSF induces iNOS expression in skin dendritic cells by a mechanism involving activation of the NF-kappaB pathway.

Animals↗
PubMed2000

Photosensitivity to lomefloxacin. A clinical and photobiological study.

Photosensitivity is an uncommon but characteristic side effect of quinolones, with a variable incidence for the different drugs. Several cases, considered either phototoxic or photoallergic, have been described with lomefloxacin use. During the last 4 years we studied 8 patients (mean age 69.4 years) with eczematous or acute sunburn-like lesions in photo-exposed areas, after taking lomefloxacin for a period of one week to several months. After drug withdrawal and systemic and/or topical corticosteroids, lesions cleared within one week to two months, with dischromia in one patient. Six to eight weeks thereafter, a photobiological study was performed. Minimal erythema dose (MED) for UVA and UVB were normal and photopatch tests with lomefloxacin, ofloxacin, ciproflaxacin and norfloxacin, tested at 1%, 5% and 10% in petrolatum and irradiated with 5 and 10 J/cm2 UVA were negative in 7 patients and 20 controls. Patient 1 had a positive photopatch test with lomefloxacin. One patient, who inadvertently reintroduced the drug before photopatch testing, developed a sharply limited erythematous reaction at 48 h in all irradiated areas, without aggravation at the sites of the quinolones patches. Our patients illustrate the polymorphism of clinical photosensitivity to lomefloxacin and represent the largest series in which photobiological studies have been performed. As in previous reports there are arguments favouring photoallergy, but phototoxicity appears to be the main mechanism of photosensitivity to quinolones, particularly in older patients with concomitant diseases and long-term use of the drug.

Adult↗
PubMed1999

Involvement of JAK2 and MAPK on type II nitric oxide synthase expression in skin-derived dendritic cells.

In this report, we demonstrate that a fetal mouse skin-derived dendritic cell line produces nitric oxide (NO) in response to the endotoxin [lipopolysaccharide (LPS)] and to cytokines [tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF)]. Expression of the inducible isoform of NO synthase (iNOS) was confirmed by immunofluorescence with an antibody against iNOS. The tyrosine kinase inhibitor genistein decreased LPS- and GM-CSF-induced nitrite (NO(-2)) production. The effect of LPS and cytokines on NO(-2) production was inhibited by the Janus kinase 2 (JAK2) inhibitor tyrphostin B42. The p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB-203580 also reduced the NO(-2) production evoked by LPS, TNF-alpha, or GM-CSF, but it was not as effective as tyrphostin B42. Inhibition of MAPK kinase with PD-098059 also slightly reduced the effect of TNF-alpha or GM-CSF on NO(-2) production. Immunocytochemistry studies revealed that the transcription factor nuclear factor-kappaB was translocated from the cytoplasm into the nuclei of fetal skin-derived dendritic cells (FSDC) stimulated with LPS, and this translocation was inhibited by tyrphostin B42. Our results show that JAK2 plays a major role in the induction of iNOS in FSDC.

Animals↗
PubMed1997

Contact allergy to gold sodium thiosulfate. A comparative study.

During 1995, we added gold sodium thiosulfate and potassium dicyanoaurate to the patch test standard series. Our purpose was to compare the reactivity of the gold salts, to determine the frequency of contact allergy to gold in our country, to compare our results with those of the Malmö group and, finally to try to clarify the clinical relevance 2853 patients were routinely tested and 168 patients answered a questionnaire similar to that used by the Malmö group. Contact allergy to gold was found in 23 patients, all women: 22 to gold sodium thiosulfate (0.78%), only 1 to potassium dicyanoaurate and 2 to both salts. All reactors had their ears pierced and were exposed to gold jewelery (mainly earrings). Simultaneous allergies to nickel and cobalt were statistically significant in patients with positive patch tests to gold sodium thiosulfate. Atopy was no more common among these patients.

Chi-Square Distribution↗