PubMed Health⌕ Search

Biomedical subjects

P Cordiali-Fei

Publications and source records attributed to P Cordiali-Fei.

At least 19 recordsLinked to original sources

Vascular endothelial growth factor gene polymorphisms increase the risk to develop psoriasis.

We investigated the relationship between eight polymorphisms in the gene encoding for vascular endothelial growth factor (VEGF) (-1540C > A, -1512Ins18, -1451C > T, -460T > C, -160C > T, -152G > A, -116G > A and +405G > C) and plaque-type psoriasis stratified for age at onset, gender and family history of dermatosis. For this purpose, 117 patients with chronic plaque-type psoriasis and 215 healthy subjects were enrolled. We found that being homozygous -1540AA, -1512InsIns, -1451TT, -460CC and -152AA conferred a significant risk in developing psoriasis compared with heterozygous (-1540CA, -1512 + Ins, -1451CT, -460CT and -152AG) and homozygous genotypes (-1540CC, -1512 + +-1451CC, -460TT and -152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively]. Conversely, having the -116AA or +405GG genotype did not significantly increase the risk of disease expression compared with other genotypes of the same loci. Interestingly, we found that -1540AA, -1512InsIns, -1451TT, -460CC and -152AA homozygous genotypes have a significant two-fold increased risk in developing psoriasis after the age of 40 years (late-onset psoriasis) (ORs = 2.19, 2.19, 2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as compared with controls. On the contrary, we found no phenotype-genotype association of the same magnitude among the patients in whom psoriasis developed at or before the age of 40 years (early-onset psoriasis) compared with controls. Genotype distributions were not significantly different when cases and controls were stratified either by gender or family history of psoriasis. Finally, VEGF plasma concentration was not significantly different between patients and controls and was not correlated with the severity of the disease.

5' Untranslated Regions↗

Cytokine profiles during infliximab monotherapy in psoriatic arthritis.

BACKGROUND: Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)-alpha antagonists such as infliximab and etanercept are the most promising as TNF is considered to be essential in driving cytokine cascade at sites of cutaneous and synovial inflammation in this disease. OBJECTIVES: To evaluate the time-related response of serum cytokine release during infliximab monotherapy and assess serum cytokine levels in order to provide a fast, minimally invasive tool to monitor and/or predict efficacy of anti-TNF-alpha therapy. METHODS: Twenty patients affected by PsA with Psoriasis Area and Severity Index (PASI) score between 0.4 and 42.8 were treated with infliximab for 30-42 weeks. The assessment of arthritis severity was performed using the American College of Rheumatology (ACR) criteria and ultrasonography evaluation. The treatment schedule consisted of infliximab (5 mg kg(-1) intravenously) at 0, 2 and 6 weeks and every 12 weeks on an individual basis determined by therapeutic results and adverse events reported. At baseline and before every infusion blood samples were taken to assess serum cytokine levels [TNF-alpha, interleukin (IL-6), E-selectin, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase (MMP-2)]. RESULTS: Eighteen of 20 psoriatic patients achieved > 50% improvement and 14 of 20 patients attained > 75% improvement in the PASI score at 10 weeks. All arthritic patients achieved > 50% improvement (ACR-50) and 16 of 20 patients attained > 75% improvement (ACR-75) at 10 weeks. TNF-alpha did not decrease immediately during the first part of the study. A significant decrease was detected at week 12 (P < 0.01). In contrast, IL-6, VEGF, FGF and E-selectin showed significant decreases after early infliximab infusions. PASI was not correlated with TNF-alpha in the serum but was significantly correlated with FGF, VEGF and MMP-2. Treatment was well tolerated and there were no significant adverse events in most patients, other than an urticarial reaction and an autoimmune hepatitis. CONCLUSIONS: Monotherapy with infliximab has to be considered an efficacious and safe treatment for PsA in comparison with traditional disease-modifying antirheumatic drugs. The resolution of cutaneous and synovial symptoms is not related to TNF-alpha serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response.

Adult↗

Development of a novel ELISA system for detection of anti-BP180 IgG and characterization of autoantibody profile in bullous pemphigoid patients.

BACKGROUND: The NC16A immunodominant region of the bullous pemphigoid (BP) antigen BP180 has been used to develop several enzyme-linked immunosorbent assays (ELISAs) as diagnostic tools for BP autoantibody detection. OBJECTIVES: Because BP180 autoantibody reactivity is not restricted to NC16A, we have investigated the possibility of developing an ELISA based on selected epitopes additional to this immunodominant region. METHODS: Initially 78 BP sera were tested using an NC16A ELISA and IgG reactivity was detected in 64 BP sera (82%). The 14 NC16A-negative BP sera were then analysed by immunological screening against seven BP180-specific epitopes. Recombinant phages displaying BP180 epitopes were grown as plaques, blotted onto a nitrocellulose filter and incubated with BP sera. RESULTS: Three and five NC16A-negative BP sera reacted with epitopes AA 1080-1107 and AA 1331-1404 of the BP180 ectodomain, respectively. Thus, a novel ELISA with GST-1080 and GST-1331 (GST-1080/1331) was developed: 32 of 78 BP sera (41%) proved positive by this assay. The combined use of ELISAs with GST-NC16A and GST-1080/1331 detected IgG reactivity in 72 of 78 BP sera, increasing the sensitivity from 82% to 92%. In addition, autoreactivity against the three extracellular epitopes appeared to be related to the presence of both skin and mucosal involvement as assessed by Fisher's exact probability test. CONCLUSIONS: Our findings further characterize the autoimmune response in BP by identifying a subgroup of NC16A-negative patients who react with different BP180 extracellular epitopes. The developed ELISA system appears more sensitive than the ELISA based on NC16A alone and also informative about the epitope profile of BP patients.

Adult↗

Increased tryptase and myeloperoxidase levels in blister fluids of patients with bullous pemphigoid: correlations with cytokines, adhesion molecules and anti-basement membrane zone antibodies.

Tryptase and myeloperoxidase respectively represent 2 specific markers of activated mast cells or neutrophils. Therefore, establishing the levels of these enzymes may be useful to quantify the cell involvement in the tissues or fluids of different origins and in different pathologies. The aim of this study was to analyse the levels of these 2 markers in both the sera and blister fluids of patients affected with bullous pemphigoid. These levels were then correlated to the concentrations of 19 cytokines and 2 soluble adhesion molecules determined in the same samples and also with the log (anti-basement membrane zone antibody) titres, evaluated in the patients' sera. For these purposes, 15 patients with bullous pemphigoid (10 males and 5 females; median age: 84 years, range 66-87; median disease duration: 0 years, range 0-3: median number of skin lesions: 17, range 14-30; median anti-basement membrane zone antibody titre: 1:320, range 0.0-1:2560) and 15 normal subjects (11 males and 4 females, median age: 81 years, range 59-86) were analysed by means of commercially available kits. Results showed that blister fluid myeloperoxidase and tryptase levels were increased as compared with the respective sera (P<0.01) and several correlations were observed with cytokines and adhesion molecules. In fact, significant correlations of blister fluid tryptase levels were observed with IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, VEGF, RANTES and sICAM-1, while myeloperoxidase was correlated with IL-1beta, IL-13 and IL-15. The blister fluid tryptase levels were also significantly correlated with the anti-basement membrane zone antibody titres (R=0.53, P=0.05). In conclusion, these findings are in accord with an involvement of both mast cells and neutrophils in bullous pemphigoid and their recruitment may be mediated by different biological modulators. Our findings seem to indicate that the cytokine (IL-3, IFN-gamma and OSM) or adhesion molecule (sICAM-1) concentrations in blister fluid are logarithmically related to the anti-basement membrane zone antibody titers.

Aged↗

Heterogeneity of oral isolates of Candida albicans in HIV-positive patients: correlation between candidal carriage, karyotype and disease stage.

Opportunist infections involving Candida albicans often develop in HIV-positive patients and oral lesions tend to become more frequent as the disease progresses. Previous studies have shown contrasting results concerning the variability of the pulsed-field gel electrophoresis (PFGE) subtypes of C. albicans observed in HIV-positive patients. Carriage of C. albicans was determined by an oral rinse technique; 41 strains of C. albicans (78% serotype A and 22% serotype B) were isolated. There was a direct correlation between candidal load (cfu/ml) and the blood HIV load, whereas there was an inverse correlation with the stage of disease and the CD4 cell counts. The PFGE patterns of isolates were variable with regard to the number and positions of bands. The variability of the band sizes in some run positions showed a Gaussian distribution. Generally, the most frequent size variants were associated with the strains with the highest cfu/ml and lowest CD4 counts (< or =200 cells/microl). These findings suggest a possible strain selection over time during disease progression, especially in HIV-positive subjects with low CD4 counts.

AIDS-Related Opportunistic Infections↗

Identification of a new control region in the genome of the DDP strain of BK virus isolated from PBMC.

The various strains of human polyomavirus BK (BKV) show a marked heterogeneity in the non-coding control region (NCCR), which includes the origin of replication and the regulatory region for early and late transcription. A new BKV strain (DDP, U91605) was identified by direct detection and sequencing of PCR products of BKV-NCCR DNA obtained from PBMC samples of HIV-positive or -negative subjects. The DDP strain NCCR sequence showed an organisation not described previously in vivo with the maximum homology with the archetypal strain (WW) (M34048), as compared with those collected in GenBank. Structurally, P68, Q39, and S68 boxes were perfectly conserved, whereas the R63 box was completely deleted. This deletion involves the loss of sequences able to bind cellular factors essential for the DNA transcription, such as NF1 binding sites, normally present twice in the R box and the modification of SP1. It is possible that these rearrangements represent a cause of the loss of the VP1 region observed in 9/22 PBMC samples and never observed in urine isolates, which are similar to the WW strain.

BK Virus↗

Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10.

This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF-beta1 in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations (P<0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no significant TGF-beta1 variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity (r=0.64, P=0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts (r=0.80, P<0.001) and antibodies directed against the basement membrane zone (r=0.65, P<0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at the local level (keratinocyte is known to produce IL-7 and the latter is known to be down-regulated by IL-10, and in other models also by TGF-beta1 and IL-4, whose levels are elevated in BP BFs) as opposed to an increased peripheral release of the same modulator. The IL-7 reduction may have a biological relevance in controlling a chronic, progressive disease.

Adult↗

Increased interleukin-7 concentrations in lesional skin and in the sera of patients with plaque-type psoriasis.

Several cytokines have been shown to be increased in psoriasis, mainly at the local and sometimes at the systemic level. At present, no data concerning the relationships between psoriasis and interleukin-7 (IL-7) are available. This biological modifier regulates immune response by means of its pleomorphic activities, including the ability to stimulate different monocyte functions, such as killing of intracellular pathogens, induction of cytokines, and enhancement of some membrane molecule expression. Study groups consisted of nine psoriatic and nine normal subjects. Using a commercially available immune-enzyme method, IL-7 concentrations were determined in various samples: biopsy and scale extracts, peripheral blood mononuclear cells (PBMCs) supernatants, and sera. The results show that IL-7 levels are significantly increased both in biopsy and in scale extracts obtained from lesional skin compared to those obtained from nonlesional and normal skin (P at least < 0.01). In addition, the serum values were higher in psoriatic patients than in the controls (P = 0.003). In contrast, no significant differences were observed in the supernatants of unstimulated PBMCs maintained in culture for 48 hr. These data suggest that IL-7 is involved in some way in the pathomechanisms of psoriasis and that the keratinocyte may be a candidate for psoriatic IL-7 overproduction.

Adult↗

Use of discriminant analysis to assess disease activity in pulmonary tuberculosis with a panel of specific and nonspecific serum markers.

Several cell activation markers, acute phase reactants, enzymes, and antituberculous antibody serum levels have been proposed as possible markers to monitor disease activity in patients with tuberculosis. They have all shown limited sensitivity or specificity. The authors therefore attempted to generate a canonical variable using discriminant analysis, including sensitive and specific parameters, to be a reliable marker in classifying patients correctly during the course of pulmonary tuberculosis. The following parameters were selected: two soluble cell activation markers (soluble interleukin-2 receptor and sCD8); the levels of immunoglobulin (Ig) G and IgM antibodies against the A60 antigen complex; and the presence of specific antibodies directed to eight different A60 components, revealed by Western blot analysis. The tests were performed on sera from three groups of patients with pulmonary tuberculosis. The first group comprised 25 patients with onset tuberculosis, clinically active (OTCA), evaluated at the time of admission. The second group included 28 patients with chemotherapy-treated tuberculosis, clinically active (CTCA), 2 months after therapy had begun. The third group included 20 patients with tuberculosis, nonclinically active (TNCA), who had had at least 1 year of effective therapy. The authors obtained an 80.9% rate of correct classification for the three groups and a rate of 100% when OTCA and TNCA were compared. The patients with CTCA were scarcely differentiated and tended to be distributed into the two other groups. To improve the separation between patients with CTCA and those with OTCA, a second canonical variable was generated with a 91.7% rate of correct classification, as compared with 71% obtained using the sCD8 as the best single variable. The mean values of the last canonical variable were statistically different (Mann-Whitney test, P = .049) when stratified for acid fast bacilli-positive or negative CTCA patients (microscopic detection). Three patients, followed during the entire course their disease, were, as expected, correctly positioned with respect to the subsequent disease phases.

Adult↗

Detection of HIV genome in HIV antibody negative men.

The presence of the human immunodeficiency virus (HIV) genome was investigated by applying in situ hybridisation techniques to peripheral blood mononuclear cells (PBMCs). Twenty asymptomatic anti-HIV seronegative homosexual men were the subjects of our study. The cells were hybridised with: (1) an SP 64 plasmid containing the nine-kilobase SstI-SstI viral insert from the lambda BH 10 recombinant clone; this can recognise both viral RNA and proviral DNA, and (2) with a pA01 plasmid containing HBV DNA genome. The DNA probes were modified by inserting an antigenic sulfone group in the cytosine moieties and the visualisation was performed by a double antibody immunohistochemical reaction. In two subjects both the HIV genome and HBV DNA were detected whereas another two subjects were positive for HBV DNA and for the HIV genome respectively. Thus people who are seronegative for anti-HIV specific antibodies may be infected with HIV.

Adult↗

Accessory cell function of human melanoma cells in mitogen-induced T cell proliferation.

Six out of eight human melanoma cell lines were found to be able to function as accessory cells in PHA-induced proliferation of autologous and allogeneic T cells. The accessory cell function of the melanoma cell lines appears to be similar to that of monocytes, requires the presence of viable cells, and does not correlate with the cell surface binding sites for PHA and with the level of expression of HMW-MAA and of HLA Class I antigens. HLA Class II antigens do not appear to play a major role in these phenomena, since there is no relationship between level of expression of HLA Class II antigens and accessory cell function of melanoma cells. Furthermore, addition of anti-HLA Class II monoclonal antibodies does not affect proliferation of T cells stimulated with PHA in the presence of melanoma cells with accessory cell function. Although melanoma cells exert accessory cell function, functional and immunological assays did not detect IL-1 in the spent medium of the melanoma cell lines. Furthermore, Northern blotting analysis with IL-1 alpha and IL-1 beta probes did not detect IL-1-specific mRNA in melanoma cell lines. These results suggest that PHA-induced proliferation of T cells in the presence of melanoma cells can bypass the requirement for IL-1 or utilizes factors other than IL-1.

Antigen-Presenting Cells↗

Levels of Ia-like antigen bearing lymphocytes in patients with solid primary tumors.

In patients with different types of solid tumors who had no detectable metastasis and had received no radio- and chemotherapy the levels of Ia-like antigen bearing lymphocytes was determined by indirect immunofluorescence staining of peripheral lymphocytes with xenoantisera to framework determinants of Ia-like antigens. The level of Ia-like antigen bearing lymphocytes was increased in patients with urinary bladder carcinoma, was decreased in patients with carcinoma of the gastrointestinal tract and was within normal ranges in patients with melanoma, carcinomas of the breast, lung and genital tract. In patients with carcinomas of the gastrointestinal tract as well as in patients with carcinoma of lung and genital tract the levels of T lymphocytes measured by rosetting with sheep red blood cells, was reduced while it was not different from normal in other groups of patients. Determination of the level of lymphocyte subpopulations may provide information about the immunocompetence status of patients with solid tumors.

Adult↗

Specific and aspecific immune responsiveness in lung cancer patients: cutaneous delayed hypersensitivity reactions to a lung cancer-associated antigen.

The ability of a lung cancer-associated antigen (LCAA) to provoke specific cutaneous delayed-hypersensitivity reactions has been studied on a group of 59 lung cancer patients. Biological activity of LCAA, monitored by skin testing, was demonstrated in 32% (17 of 53) of lung cancer patients, in 48.0% with limited disease, and in 17.2% with extensive disease. All the responders were in the group of normal reactors to standard recall antigens, if three antigens were used (PPDSK-SD, candida). No correlation was found between biological activity of LCAA and level of immunocompetence evaluated by lymphocyte-blastic transformation with PHA and count of rosette E-forming cells. These studies on the capacity to evoke specific DTH reactions in lung-cancer patients will be extended to the use of assays in vitro in the perspective of a more significant evaluation of immunocompetence levels.

Antigens, Neoplasm↗

Occurrence of globulin-like migrating blood albumins, or GLIMBAL, in pathological rat and human sera.

The presence in the serum of albumins having a globulin-like electrophoretic mobility (globulin-like migrating blood albumins or GLIMBAL) has been determined by immunoelectrophoresis in rat and human sera. GLIMBAL have been detected occasionally (14%) in rat sera during the acute inflammation induced by yeast injection. GLIMBAL were, on the other hand, present in pathological human sera from patients with rheumatoid arthritis (50%), systemic lupus erythematosus (69%), and liver disease (17%). These data indicate that the occurrence of GLIMBAL in human sera is more frequent than previously described. Many pathological conditions are accompanied by electrophoretic changes of serum, consisting of an increase of globulins and eventually albumin decrease; our data indicate that these changes may in some conditions reflect a process of albumin transformation rather than an increase in globulin synthesis.

Animals↗

Immunologic monitoring during combined radiochemoimmunotherapy in inoperable lung cancer.

49 patients with advanced lung cancer underwent a combined treatment including radiochemoimmunotherapy. Before and at the end of the combined treatment, the immune status of the patients has been evaluated by testing the immunoreactivity to PPD in vivo and the phytohemagglutinin lymphocyte response and the rosette-forming cells in vitro. While the in vitro tests were not significantly modified by immunostimulation, as regards the immunoreactivity to PPD, we observed a positive conversion at the end of the treatment in 11 out of 25 patients who showed a negative reaction before therapy. All the patients who converted from negative to positive showed also a good response to therapy with regression or no progression of the tumor. Survival curves confirmed the prognostic value of PPD reactivity.

BCG Vaccine↗

Estimation of PHA induced transformation in peripheral blood lymphocytes through measurement of their increased glycolysis. An enzymatic micromethod.

Peripheral blood lymphocytes undergoing blast transformation after contact with PHA, show a rapid increase in glycolysis. The phenomenon can be quantitated by measuring the amount of lactate released in the culture medium. This measurement has been adapted to a micromethod which allows the study of PHA induced transformation in a large number of samples in a short time. The present method which avoids the use of radioisotopes correlates in 90% of the cases with the 3H-thymidine incorporation test.

Adolescent↗