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Biomedical subjects

J Font

Publications and source records attributed to J Font.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

Human epidermis reconstructed on synthetic membrane: influence of experimental conditions on terminal differentiation.

Cell suspensions of human keratinocytes seeded onto cell culture inserts may undergo terminal differentiation in the absence of fibroblasts. Among the parameters that control these morphogenic events, exposure to air and the composition of the culture medium were investigated. In the latter case, three media were considered DMEM:Ham's F12, MCDB 153, and keratinocyte SFM medium at equivalent calcium (1.5 mM) and fetal calf serum (5%) concentrations. Immunochemical methods and transmission electron microscopy show that cells cultured in DMEM:Ham's F12 medium, and then raised at the air-liquid interface, form a basal layer plus suprabasal cell layers corresponding to the stratum spinosum, stratum granulosum, and stratum corneum. The suprabasal keratinocyte layers show morphologies that resemble intact skin in which cells are connected by desmosomes and contain intermediate filaments and keratohyalin-filaggrin granules. When the cultures are kept submerged, the keratinocytes show occasional keratohyalin granules and are connected by fewer desmosomes. Additionally, no proper stratum corneum is formed. In keratinocyte SFM medium and MCDB 153, cultures raised at the air-liquid interface are not able to form an epithelium of normal architecture and do not express terminal differentiation markers. Differentiation is initiated, however, since desmosomes and bundles of keratin filaments appear; on the other hand, filaggrin is not expressed even after 28 d in culture. Membrane-bound transglutaminase is expressed throughout the entire suprabasal compartment in MCDB153 and DMEM:Ham's F12 media but never appears in keratinocyte SFM medium. These studies show the relative independence of epidermal differentiation program to the composition (including the calcium concentration) of the media contacting the dermis and filling the extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMedDate not supplied

Bcl-2 oncogene (B cell lymphoma/leukemia-2) levels correlate with systemic lupus erythematosus disease activity.

OBJECTIVE: Bcl-2 translocation or overexpression is found in many types of malignancy, possibly through alteration of the apoptosis mechanism. It has also been suggested that similar apoptotic alterations may be important in the pathogenesis of systemic lupus erythematosus (SLE). It is believed that a process of apoptosis at the stage of maturation or differentiation of lymphocytes may be related to the beginning of an autoimmune event, due to the non-elimination of autoreactive lymphocytes. The aim of this study is to test bcl-2 antigen expression in human SLE peripheral blood and to analyze its relationship with disease activity. MATERIALS AND METHODS: Serum levels of bcl-2 were studied by enzyme-linked immunoabsorbent assay in whole blood samples in 68 patients with SLE and its correlation with disease activity according to SLE disease activity index (SLEDAI). RESULTS: No significant differences were found in bcl-2 levels between all SLE patients and controls. We observed increased levels of bcl-2 in active SLE patients in relation to inactive (p = 0.0003) and controls (p = 0.02). Our results show a significant correlation between bcl-2 levels and SLEDAI values (R = 0.46, P < 0.001). CONCLUSIONS: These results suggest that bcl-2 levels are related to disease activity and that this protein may play a role in the pathogenesis of SLE.

Adolescent↗
PubMedDate not supplied

Circulating levels of Th1/Th2 cytokines in patients with primary Sjögren's syndrome: correlation with clinical and immunological features.

OBJECTIVE: To analyse the circulating levels of Th1 and Th2 cytokines in patients with primary Sjögren's syndrome (SS), as well as to investigate their association with clinical and immunological manifestations. METHODS: We included 62 consecutive patients (58 women and 4 men) seen in our Unit. All patients fulfilled 4 or more of the European diagnostic criteria for SS. Serum levels of IL-6 (pg/mL), IL-2 (pg/mL), srIL-2 (pM), TNFalpha (pg/mL) and IL-10 (pg/mL) were determined using a solid phase enzyme immunoassav performed on microtiter plate. RESULTS: When compared with the control group, high levels of Th1 (11-2, srIL-2) and Th2 (IL-6, IL-10) cytokines were detected in SS patients, although only IL-6 levels reached statistical significance. On the other hand, analysis of the mean serum concentrations of cytokines showed distinct patterns of elevated cytokines according to the organ involved, and elevated levels of IL-6 (126.5 v 20.6 pg/mL, p < 0.05) and IL-10 (10.6 v 2.2 pg/mL, p < 0.005) were observed in those patients with liver involvement. Analysis of the cytokine levels according to the presence of immunological features showed: higher levels of srIL-2 (95.6 v 54.0 pM, p < 0.05) in patients with anti-Ro/SS-A antibodies; increased levels of srIL-2 (111.4 v 59.4 pM, p < 0.05) in patients with antiLa/SS-B antibodies; higher levels of srIL-2 (90.4 vs 50.8 pM, p < 0.05) and TNFalpha (37.9 v 22.6 pg/mL, p = 0.001) in patients with RF and higher levels of IL-6 (88.0 v 23.1 pg/mL, p < 0.05) in patients with cryoglobulins and in those with hypocomplementemia (130.3 vs 21.0 pg/mL, p < 0.05). CONCLUSION: We found a significant elevation of several circulating cytokines in some clinical and immunological subsets of patients with primary SS. These cytokine patterns may be markers for specific extraglandular involvement in SS and could be of interest in assessing the response to treatment protocols or in monitoring the disease evolution.

Adult↗
PubMedDate not supplied

Relationship of oncogenes (sFas, Bcl-2) and cytokines (IL-10, alfa-TNF) with the activity of systemic lupus erythematosus.

BACKGROUND: Different oncogenes (Fas and bcl-2) and diverse cytokines (IL-10 and alfa-TNF) may have an effect on the regulation of apoptosis. The majority of studies to date have evaluated only one or two of these elements independently and it is difficult to obtain a global view of apoptosis disregulation in the pathogenesis of systemic lupus erythematosus (SLE) and their role in disease activity. The aim of this study was to evaluate serum levels of sFas, bcl-2, IL-10 and alfa-TNF in human SLE patients and to analyze their relationship with disease activity and with regulation of the apoptotic process. PATIENTS AND METHODS: Serum levels of sFas and cytokines IL-10 and alfa-TNF were studied by enzyme-linked immunoabsorbent assay. Bcl-2 antigen expression was analyzed in lysated lymphocytes from 51 SLE patients. The disease activity was analyzed according to the SLE disease activity index (SLEDAI). RESULTS: SLE patients had higher levels of sFas (p=0.0006) and alfa-TNF (p<0.0001) than the control group. No relationship was found between the levels of bcl-2 and IL-10 from SLE patients and the control group. However, there was a significant correlation between SLEDAI and bcl-2 (p<0.001) and IL-10 levels (p=0.004). In contrast, we found that sFas and alfa-TNF were not related with disease activity. A significant correlation of sFas with alfa-TNF serum levels (p=0.003, R= +0.41) and bcl-2 antigen expression (p=0.02, R=+0.32) was observed. CONCLUSION: sFas and alfa-TNF serum levels are increased in SLE patients. sFas levels seems to be secondary to alfa-TNF action, which is enhanced in inflammatory conditions such as SLE. Bcl-2 antigen expression and IL-10 serum levels are related to the maintenance of SLE activity. These alterations may interfere with the apoptotic process, promoting lymphocyte hyperactivity secondary to increased cytokine levels, and causing the characteristic features of SLE.

Adolescent↗
PubMedDate not supplied

Low values of creatine kinase in systemic lupus erythematosus. Clinical significance in 300 patients.

OBJECTIVE: To study creatine kinase (CK) activity in a large series of patients with systemic lupus erythematosus (SLE) and identify the clinical and immunological features related to reduced levels. METHODS: In a cross-sectional study, serum CK activity was measured in 300 consecutive patients with SLE (271 females and 29 males, with a mean age of 36 years). All patients fulfilled the 1982 revised criteria of the American College of Rheumatology. RESULTS: Low serum CK levels (< 33 IU/L) were detected in 118 (39%) of SLE patients. When compared to SLE patients with normal serum CK levels, those with SLE and low serum CK levels had a higher frequency of fever (53% vs. 34%, p = 0.017), renal involvement (43% vs. 27%, p = 0.004), and hemolytic anemia (13% vs. 6%, p = 0.037). In addition, SLE patients with low CK values also presented lower values of hemoglobin, total proteins, albumin, cholesterol and triglycerides, higher values of ESR and low C3 (44% vs. 27%, p = 0.004), C4 (57% vs. 37%, p = 0.001) and CH50 levels (60% vs. 41%, p = 0.02). We analysed in 69 patients the correlation between CK and 24-hour proteinuria values, and found that those with a 24-hour proteinuria > 1500 mg/day showed lower CK values than those with proteinuria < 1500 (31.95 vs 63.84 IU/L, p = 0.046). CONCLUSION: We observed that serum CK levels were reduced in 39% of SLE patients. Reduced serum CK activity was significantly related to some clinical (fever, nephropathy), hematological (high ESR, hemolytic anemia) and immunological (hypocomplementemia) features, which relate to disease activity. This suggest that reduced CK activity might be inversely correlated to inflammatory activity in SLE.

Adult↗
PubMedDate not supplied

Influence of clinical and immunological parameters on the health-related quality of life of patients with primary Sjögren's syndrome.

OBJECTIVE: To evaluate health-related quality of life (HR-QoL) in patients with primary SS patients using the SF-36 questionnaire and to analyse the association between the main clinical features and the SF-36 scales. METHODS: We studied 110 patients (105 women and 5 men, mean age of 56 years) with primary SS seen consecutively in the outpatient clinic of our Department. We used the population-based reference values for the Spanish version of the SF-36 health survey as control values for a healthy population. RESULTS: Comparison between patients with primary SS and the control population showed lower scores in all SF-36 scales (p < 0.001). Analysis of the SF-36 scales by gender showed a significant correlation between age and the values for physical functioning (p = 0.013) and bodily pain (p = 0.016) scores. No significant differences in SF-36 scores were found when comparing patients according to the presence or absence of sicca features. Women with vaginal dryness had lower scores for social functioning (61.9 vs. 74.4) and general health (37.2 vs. 44.7) than those without, although the differences were not statistically significant (p > 0.05). Patients with extraglandular involvement had lower scores for the vitality scale (40.8 vs. 54.5 p = 0.007), social functioning (67.0 vs. 79.8, p = 0.010), bodily pain (49.5 vs. 62.5, p = 0.018) and general health (38.6 vs. 49.4 p = 0.001) than those without. CONCLUSION: Patients with primary SS had clearly lower HR-QoL scores than the healthy population; with significantly lower scores in all SF-36 scales and in both summary measures. We identified several epidemiological and clinical SS features related to these lower SF-36 scores. Age at protocol correlated with physical functioning and bodily pain. Vaginal dryness was the sicca feature that most affected the HR-QoL of female SS patients, and a poor HR-QoL was also observed in those patients with a systemic expression of the disease, with pulmonary involvement being the extraglandular manifestation that most contributed to a poor HR-QoL. Our results highlight the importance of earlier diagnostic and therapeutic management of patients with primary SS, which, together with a close follow-up, may contribute to a significant improvement in their HR-QoL.

Female↗
PubMedDate not supplied

Behçet's disease and hereditary periodic fever syndromes: casual association or causal relationship?

OBJECTIVE: Mutations in the MEFV and the type 1 TNF receptor (TNFRSF 1A) genes have recently been linked to familial Mediterranean fever (FMF) and TNF receptor-associated periodic syndrome (TRAPS), respectively. A higher prevalence of Behçet's disease (BD) among FMF patients has been described compared to the general population. The aim of this study was to evaluate whether FMF TRAPS and BD could be genetically related. METHODS: We screened a cohort of 50 BD patients and 100 healthy subjects for the common MEFV and TNFRSF 1A mutations. An initial screening of exons 10 and 2 of the MEFV gene and exon 4 of the TNFRSF 1A was performed in all chromosomes. RESULTS: The heterozygous MEFV mutation (K695R) was found in one (2%) BD patient. Analysis for FMF mutations in the control group revealed that 5 (5%) individuals bore MEFV gene mutations (3 were heterozygous for the E148Q and 2 were heterozygous for the A744S). At codon 202, there were no differences in allele frequencies between BD and control population: 73%R 27%Q in the BD patients vs 75%R 25%Q in controls. Concerning mutations in the TNFRSF 1A gene, the R92Q mutation was present in heterozygous state in one (2%) BD patient and in 4 (4%) controls without differences between allele frequencies: 99%R 1%Q in BD patients vs 98%R 2%Q in controls, respectively. There was no association between the clinical manifestations of BD patients and the presence of a particular polymorphism or a mutation. CONCLUSIONS: Neither FMF nor TRAPS are genetically associated with BD in our cohort of Spanish patients.

Behcet Syndrome↗
PubMedDate not supplied

Late thrombotic events in patients with temporal arteritis and anticardiolipin antibodies.

IgG and IgM isotypes of anticardiolipin (aCL) antibodies were measured in a group of 40 patients with biopsy-proven temporal arteritis (TA), 13 of them with ischemic complications related to the disease. High levels of aCL antibodies were found in only 3 (7.5%) patients. Two had high titres of both IgG and IgM isotypes and the third had high titres of the IgM isotype. No relationship between aCL antibody positivity and the development of any of the classical early occlusive complications of TA was found. However, 2 out of the 3 patients with positive aCL antibody titres later developed ischemic phenomena on conventional corticosteroid treatment. This finding suggests that aCL antibodies could perhaps have a role in the development of the late ischemic complications that occasionally occur in adequately treated TA patients.

Aged↗
PubMedDate not supplied

Diagnostic interest of the monoclonal antibody CA1 in malignant pleural effusion.

The Ca1 antibody was used in an immunohistochemical procedure on smears of cells from 40 patients with malignant pleural effusion. The control group consisted of 25 benign pleural effusions with a high percentage of reactive mesothelial cells. The Ca1 Mc Ab was positive in 19 (79%) of the 24 pleural effusions with positive malignant cytology. In all the benign cases the Ca1 Mc Ab was negative (100% specificity). The Ca1 Mc Ab detected malignant mesothelial cells in two cases and was negative with reactive mesothelial cells and other nucleated cells present in the pleural effusion. We conclude that the Ca1 antibody offers a useful diagnostic method for malignant pleural effusions, when the morphological interpretation is doubtful.

Antibodies, Monoclonal↗