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Biomedical subjects

F Ameglio

Publications and source records attributed to F Ameglio.

At least 55 records · Page 3Linked to original sources
PubMed1997

The serum levels of sE-selectin are increased in patients with bullous pemphigoid or pemphigus vulgaris. Correlation with the number of skin lesions and recovery after corsticosteroid therapy.

Soluble E (sE)-selectin represents the soluble isoform of cellular E-selectin, an adhesion molecule synthesized only by endothelial cells. As a consequence, it may be considered a marker of endothelial activity. The aim of this study was therefore to evaluate the serum levels of sE-selectin in nine patients affected with pemphigus vulgaris (PV) and in 15 patients with bullous pemphigold (BP). Higher amounts of sE-selectin, median 40.3 ng/mL, range 30-109.6 were found in the patients when compared with 20 healthy individuals, median 28.5 ng/mL, range 6.4-48; P < 0.01, matched for sex and age. These levels were also significantly correlated with the number of detectable lesions (r = 0.63, P < 0.001) when the patient data were considered at the time of the first observation. Thirteen subjects were followed over time for a maximum of 3 months (from three to seven observations). During therapy, the number of lesions and the serum sE-selectin values decreased concomitantly. Differently from sE-selectin, the serum soluble intercellular adhesion molecule-1 (sICAM-1) values were not significantly different in the patients from the controls and showed no correlation with the serum sE-selectin concentrations or with the number of lesions. The data presented point to the possible use of sE-selectin determinations as a non-specific follow-up marker, suitable to gauge disease intensity over time and emphasize that endothelial activation is present in BP as well as in PV.

Administration, Topical↗
PubMed1997

Cytokines in the sera of patients with pemphigus vulgaris: interleukin-6 and tumour necrosis factor-alpha levels are significantly increased as compared to healthy subjects and correlate with disease activity.

Cytokine serum levels, when detectable, are currently measured in many disease states, both to evaluate a possible pathogenetic involvement of such molecules and for clinical purposes. No data are currently available on the cytokine levels in the sera of patients with pemphigus vulgaris (PV), a rare bullous disease of autoimmune origin. This study presents data concerning the levels of 13 different cytokines assayed in the sera of 25 patients affected with PV as compared with 20 healthy subjects using high sensitivity ELISA kits. Of the 13 molecules analyzed, no differences in the levels of most cytokines were observed between pemphigus and control sera, with the exception of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Serum TNF-alpha and IL-6 levels were found to be significantly higher in PV patients than in normal controls (p < 0.001). Furthermore, the levels of the two cytokines decreased after one month of corticosteroid therapy. A significant correlation was found between the serum levels of both TNF-alpha and IL-6 and the number of lesions for each patient (p < 0.001). The data presented support an involvement of at least IL-6 and TNF-alpha in the biological modifications associated with PV manifestations.

Adult↗
PubMed1996

Carcinoembryonic antigen, tissue polypeptide antigen and neuron-specific enolase pleural levels used to classify small-cell and non-small-cell lung cancer patients by discriminant analysis.

The classification of lung cancer into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) is essential for disease prognosis and treatment. For this purpose, we have tried to optimize the use of three tumour markers determined on pleural effusions, to differentiate SCLC from NSCLC by means of a canonic variable, generated by discriminant analysis, including subjects with histologically proven lung cancer. Discriminant analysis was performed by using carcinoembryonic antigen, neuron-specific enolase and tissue polypeptide antigen pleural levels, determined in 65 consecutive and unselected patients, histologically classified as 49 NSCLC and 16 SCLC. To validate the formula generated, a control group of 37 lung cancer patients (10 SCLC and 27 NSCLC), enrolled subsequently, was employed. Applying the discriminant analysis to SCLC and NSCLC patients a good classification was obtained (92% rate of correct classification). The aforementioned formula, applied to the validation group, showed a 92% rate of correct classification. This method, which is rapid, inexpensive and routinely applicable to malignant pleural effusions, may be reliably used to classify lung cancer patients.

Adult↗
PubMed1996

Paraphenylene diamine, a contact allergen, induces oxidative stress in normal human keratinocytes in culture.

During the course of evaluating the interaction between allergens and keratinocytes in the pre-immunological phase of contact sensitization, we have studied the effects of paraphenylene diamine (pPD) on membrane lipid peroxidation and on intracellular antioxidant levels in cultured human keratinocytes. pPD is an aromatic amine which undergoes spontaneous oxidation in culture medium, generating short-lived free radical species including oxyradicals. Following exposure to non-toxic concentrations of pPD (0.5-10 micrograms/ml), we have evaluated the fatty acid pattern of membrane phospholipids as a target of peroxidative damage, and the intracellular level of reduced glutathione (GSH), the activity of superoxide dismutase (SOD), and that of catalase (CAT) as parameters of the antioxidant system. Depending on pPD concentration and the period of exposure, peroxidative damage with a significant decrease in membrane polyunsaturated fatty acids, was detected. Concentrations between 0.5 and 2 micrograms/ml produced an initial increase and then a decrease in both SOD and CAT activities, and in the oxidation of GSH, up to 12 h. After 24 h, when all the pPD had decomposed, recovery of the initial levels of the antioxidants was detected. Concentrations over 5 micrograms/ml induced a progressive decrease in both the enzymatic activities and the GSH concentrations. These results are consistent with the view that oxidative stress can be an essential event in the pre-immunological phase of contact sensitization.

Allergens↗
PubMed1996

Minimal dose of aerosolized interferon-alpha in human subjects: biological consequences and side-effects.

Interferon-alpha (IFN-alpha) is a leucocyte-derived cytokine with pleiotropic effects on the cells of the immune system, including the ability to promote viral and microbial killing. This study was designed to evaluate the biologically active dosage of aerosolized lymphoblastoid IFN-alpha, in normal subjects and patients with chronic bronchitis, using serum 2'-5' oligoadenylate synthetase (OAS) as a marker of IFN-alpha activity. Three groups of subjects were included: two healthy groups and one of patients with chronic bronchitis. Group A (controls, n = 5) was studied in order to determine the minimal IFN-alpha dose able to induce biological effects without side-effects. IFN-alpha was given in a dose escalation trial including 0, 0.3 x 10(6), 1.0 x 10(6) and 3.0 x 10(6) IU.day-1 (5 day administration). Only the administration of 3.0 x 10(6) IU.day-1 of IFN-alpha induced a significant biological activity, increasing serum levels of OAS. Group B (controls, n = 5) and C (chronic bronchitis, n = 5) were given 3.0 x 10(6) IU.day-1 (10 day administration) in order to study serum, bronchoalveolar lavage fluid (BALF) and BALF cell modifications, after treatment. OAS serum levels and nitroblue tetrazolium (NBT) reduction tests, the latter used as a measure of phagocyte cell activity, increased both in normal subjects and in patients with chronic bronchitis. No significant change of serum IFN-alpha levels was found. It is concluded that aerosolized IFN-alpha administration to the lung is well-tolerated at biologically active doses. The activity can be monitored by quantifying OAS serum levels through a simple blood test.

2',5'-Oligoadenylate Synthetase↗
PubMed1995

CD4 Lymphocyte enumeration: comparison between flow cytometry and enzyme immunoassay.

Assessment of the CD4 lymphocyte number, currently performed by flow cytometry, is one of the main laboratory tests for establishing progression to acquired immunodeficiency syndrome (AIDS). An enzyme immunoassay has recently been commercialized which can be very useful for counting CD4 cells in laboratories where flow cytometers are not available. In the present study, a comparative evaluation of CD4 positive lymphocytes with flow cytometry and the enzyme assay was made in healthy subjects (N = 30, R = 0.88, P < 0.0001), human immunodeficiency virus (HIV)-infected individuals (N = 80, R = 0.91, P < 0.0001), and patients with autoimmune diseases (N = 28, R = 0.82, P < 0.001) or psoriasis (N = 18, R = 0.76, P = 0.01). A correlation between the two methodologies was not found in psoriatic patients under treatment with cyclosporin A (N = 7, R = 0.05, not significant). Some differences could be found at low CD4 lymphocyte levels since the influence of CD4 antigen eluted from monocytes or soluble CD4 in the whole blood sample could cause overestimation of CD4 cell numbers by the enzyme assay.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Host cell antigenic profile acquired by HIV-1 is a marker of its cellular origin.

HIV-1 acquires cell membrane proteins during budding. The cell membrane proteins (CMP) profile of laboratory HIV-1 strains grown in different host cells was established, by using an immobilized antibody capture (IAC), to verify whether CMPs present on HIV-1 correlate with its host cell origin. HIV-1 grown in different cell lines incorporates cell markers such as CD3, CD19, CD14, CD31 and IL 2-R, according to the distinctive expression of these antigens on the host cells. Furthermore, also T-tropic and monocytotropic HIV-1 strains display host cell specific markers, supporting the hypothesis that virus associated CMPs are a marker of host cell origin.

Antigens, CD↗
PubMed1995

HIV type 1 grown on interferon gamma-treated U937 cells shows selective increase in virion-associated intercellular adhesion molecule 1 and HLA-DR and enhanced infectivity for CD4-negative cells.

Cellular adhesion molecules, such as ICAM-1, -2, and -3; LFA-1; and HLA class I and II are incorporated into HIV-1 virions during budding from infected cells. These virion-associated molecules can be involved in the adsorption to susceptible cells displaying the corresponding counterligands. A number of cytokines have been shown to upregulate the cellular expression of adhesion molecules, such as ICAM-1 and HLA-DR. In this study we investigated the effects of IFN-gamma on the incorporation of ICAM-1, LFA-1, and HLA-DR into mature HIV-1 progeny from chronically infected cells. The ability of such virus progeny to infect either CD4-positive or -negative cells was also investigated. The results indicate that IFN-gamma stimulates the expression of ICAM-1 and of HLA-DR on HIV-1-infected cells, whereas LFA-1 expression is unaffected. The same modifications were also observed on virus progeny, because specific MAbs to ICAM-1 and HLA-DR captured infectious HIV-1 from IFN-treated cells with higher efficiency as compared to virus from control cells, whereas virus binding to anti LFA-1 MAb was unchanged. Moreover, the HIV-1 progeny released from IFN-treated cells showed an increased ability to bind to and to infect CD4-negative cells, whereas the infectivity was basically unchanged for CD4-positive cells. Our results suggest that cytokines, as well as other soluble factors, may expand the host cell range of HIV-1, possibly through modifications of the cell-derived surface molecules on the virions.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4 Antigens↗
PubMed1995

Sequential biochemotherapy for metastatic colorectal cancer using fluorouracil, folinic acid, thymopentin and interleukin-2: clinical and immunological effects.

BACKGROUND: A phase II study was performed to evaluate the clinical and immunological effects of a regimen of fluorouracil (5-FU) and folinic acid (FA) combined with thymopentin (TP-5) and interleukin-2 (IL-2) in the treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty-five evaluable patients with measurable colorectal cancer and no prior therapy for metastatic disease were treated with 5-FU 400 mg/m2/d and FA 200 mg/m2/d i.v. on days 1-5, TP-5 50 mg s.c. on days 8-11, and IL-2 9 MU/m2 s.c. twice daily on days 12-16. Cycles were repeated at 4-week intervals if toxicity had resolved. Immunological changes were evaluated in 13 patients and compared with a well matched series of 13 patients treated with the same regimen without TP-5. RESULTS: Two complete responses and 17 partial responses were seen (42%; 95% confidence interval, 28% to 56%). Fifteen patients (33%) had stable disease. The median time to progression was 8.5 months and the median survival 13 months. Treatment was reasonably well tolerated, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Hematological and immunological changes during treatment were qualitatively similar to those expected with IL-2 +/- chemotherapy. Quantitatively, significant changes (higher levels of IL-2, CD25 and IFN-gamma, and lower levels of sIL-2R) were observed in patients given TP-5. CONCLUSION: The combination of 5-FU + FA and TP-5 + IL-2 is effective in advanced colorectal cancer with acceptable toxicity. Immunological data suggest that TP-5 may modulate the action of IL-2 in the clinical setting. However, improved treatment approaches are needed, and the interactions between thymic hormones and cytokines should be further explored.

Adult↗
PubMed1995

Correlation of lesional skin corneometry values with serum E-selectin levels and disease severity in patients affected by plaque-type psoriasis: recovery after effective therapy.

Ten subjects with plaque-type psoriasis (5 females, 5 males, median age 47, range 20-71 years, median psoriasis area and severity index [PASI] score = 15.5, range 8.1-23.0) were observed before (week 0) and at the second and sixth week after starting treatment (PASI = 10.5, range 7.8-14.6; PASI = 8.5, range 1.6-11.6, respectively). At each of these times, the patients were evaluated for both lesional and unlesional skin corneometry and serum E-selectin values, previously shown to be increased in psoriatic subjects. At time 0, both the corneometry and the E-selectin values were significantly correlated with the PASI, infiltration and desquamation scores. As expected, the corneometry was statistically higher in the unlesional than in the lesional areas (p < 0.001). After therapy, the lesion improvement was related both to the PASI scores and E-selectin level decreases (from median levels of 15.5 to 8.5 and from 18 to 13.2 ng/ml, respectively, p < 0.05) as well as to the corneometric level increases (from a median value of 34.5 to 42, p < 0.05). Considering the data obtained at all of these times, significant correlations were found between the PASI scores, lesional skin corneometry and serum E-selectin levels. In conclusion, lesional corneometry seems to represent an objective alternative method for reliably monitoring psoriatic patients.

Adult↗
PubMed1995

Induction of interleukin-10 by human immunodeficiency virus type 1 and its gp120 protein in human monocytes/macrophages.

In this study, we evaluated the effects of human immunodeficiency virus type 1 (HIV-1) and its gp120 protein on interleukin-10 (IL-10) expression in cultured human monocytes/macrophages. Infection of either 1-day monocytes or 7-day monocyte-derived macrophages with HIV-1 strain Ba-L resulted in clear-cut accumulation of IL-10 mRNA at 4 and 24 h. Likewise, treatment of these cells with recombinant gp120 induced IL-10 mRNA expression and caused a marked increase in IL-10 secretion. Monoclonal antibodies to gp120 strongly inhibited recombinant gp120-induced IL-10 secretion by monocytes/macrophages. Moreover, the addition of IL-10 to monocytes/macrophages resulted in a significant inhibition of HIV-1 replication 7 and 14 days after infection. On the whole, these results indicate that HIV-1 (possibly through its gp120 protein) up-regulates IL-10 expression in monocytes/macrophages. We suggest that in vivo production of IL-10 by HIV-primed monocytes/macrophages can play an important role in the early response to HIV-1 infection.

Base Sequence↗
PubMed1995

Soluble E-selectin and soluble tumour necrosis factor receptor (60 kD) serum levels in patients with psoriasis.

BACKGROUND: Increased tumour necrosis factor alpha has been found in psoriatic skin. This cytokine activates endothelial cells and induces the membrane E-selectin molecule (E-selectin or endothelial leucocyte adhesion molecule 1); the same cytokine is able to induce its own receptors. Since the soluble forms of E-selectin and tumour necrosis factor receptor (TNF-R, 60 kD) may be reliably measured in body fluids, these determinations have been performed in the sera of psoriatic patients. OBJECTIVE: To evaluate endothelial activation in psoriatic patients, sE-selectin has been determined in patient sera and compared with those of a control group. sTNF-R (60 kD) was also measured in the same samples. METHODS: Two commercially available enzyme immunoassay methods have been used to determine sE-selectin and sTNF-R (60 kD) in the sera of 19 patients with plaque-type psoriasis; 22 healthy subjects were used as controls. CONCLUSIONS: Significantly increased amounts of sE-selectin serum levels were found in psoriatic patients as compared to healthy controls. Moreover, a direct correlation between sE-selectin and PASI scores was observed. On the contrary, sTNF-R (60 kD) serum levels presented no increases. These data suggest that sE-selectin serum levels are a reliable marker of disease activity in psoriatic patients.

Adolescent↗
PubMed1995

Discriminant analysis on small cell lung cancer and non-small cell lung cancer by means of NSE and CYFRA-21.1.

A correct diagnosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is essential both for prognostic and therapeutic reasons. We used discriminant analysis as a method to optimize the discriminant power of serum tumour marker levels for differentiation between SCLC and NSCLC. A panel of serum markers, including neurone specific enolase (NSE), cytokeratin fragment antigen 21.1 (CYFRA-21.1), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) was obtained in 50 consecutive NSCLC and 17 SCLC. Data were analysed by the BMDP statistical program after logarithmic transformation of marker levels. The variables selected were NSE and CYFRA-21.1. Considered together, they were able to give a 97% rate of correct classification. The formula generated (canonic variable, CV) was validated on a group of seven SCLC and 22 NSCLC patients. Only two errors occurred. We therefore conclude that the canonic variable tested, based on NSE and CYFRA-21.1, provides a good discrimination between the two types of lung cancer. The method is rapid, relatively inexpensive, and based on simple serum tests.

Aged↗
PubMed1995

Unidirectional budding of HIV-1 at the site of cell-to-cell contact is associated with co-polarization of intercellular adhesion molecules and HIV-1 viral matrix protein.

OBJECTIVES: To explore the possibility that HIV-1 budding and cellular adhesion molecules co-polarize at cell-to-cell contact sites. To investigate the incorporation of host-cell-derived adhesion molecules into HIV-1. METHODS: The cellular sites involved in HIV-1 budding were examined by transmission electron microscopy. Single and double immunocytochemistry staining was used to evaluate the cellular distribution of the viral matrix protein and adhesion molecules. Quantitative flow cytometry was used to measure the cellular expression of adhesion molecules. An immunocapture technique was used to measure the presence of cell-derived proteins on HIV-1. The captured virus was measured by a p24 antigen assay. The infectivity of virus captured by monoclonal antibodies was tested by measuring the virus antigen yield in supernatants after the addition of sensitive cells. RESULTS: Released and budding HIV-1 was mainly localized at the cell-to-cell contact regions. This feature was consistent with a polarized staining for the virus matrix protein p18 at cell-to-cell contact regions. Intercellular adhesion molecules (ICAM)-1 in HIV-1-infected cells were polarized on both isolated cells and syncytia, co-localizing with HIV-1 matrix protein. HIV-1 incorporated all the adhesion molecules expressed by the host cells, although without quantitative correlation with their cellular expression. CONCLUSIONS: HIV-1 is released at cell-to-cell membrane contact sites. Both ICAM-1 and virus matrix protein co-polarized on isolated cells and syncytia at the sites involved in the recruitment of uninfected cells. The impressive concentration of ICAM at cell sites where most virions are released may account for the acquisition of these membrane proteins by the HIV-1 progeny, and may be important for the cell-mediated spread.

Antigens, CD↗
PubMed1995

Evaluation of the response to chemotherapy in patients affected with small cell lung cancer using discriminant analysis: a preliminary report.

This report represents an attempt to combine the serum levels of more tumor markers together to evaluate the response to chemotherapy in 26 patients affected with small cell lung cancer (SCLC), by means of discriminant analysis. A pilot prospective study was performed on 26 subjects affected with inoperable SCLC (18 extensive diseases, and 8 limited diseases) and treated with chemotherapy (etoposide plus cisplatin regimen). Serum levels of a panel of tumor markers: Carcinoembryonic antigen (CEA), Tissue Polypeptide Antigen (TPA), Neuron Specific Enolase (NSE) and CYFRA -21.1 were determined before starting chemotherapy and at the restaging time (after 3 months). To optimize the classification power of these markers, a discriminant analysis was done, which permitted generating two classification functions, based on Tissue Polypeptide Antigen and Neuron Specific Enolase levels able to correctly classify 25 out of 26 subjects (8 progressions and 18 non progressions). The results obtained, furtherly confirm that tumor markers are useful to evaluate the chemotherapy response and indicate a possible approach to obtain the maximum usefulness of the serum marker levels.

Adult↗
PubMed1995

Ridostin inhibits HIV-1 replication in the T lymphoblastoid cell line C8166. Possible role of altered cytokine production.

Altered cytokine production in human immunodeficiency virus 1 (HIV-1) infection is well documented and cytokine modulators are currently under investigation as possible therapeutic agents. We tested the ability of Ridostin (dsRNA preparation derived from S. cervisiae) to inhibit HIV-1 replication in acutely infected T lymphoblastoid C8166 cells. Ridostin inhibited HIV-1 replication in a concentration range that is 100-fold lower than the toxic concentration for these cells. C8166 cells spontaneously produced interferon (IFN) alpha and gamma, as well as tumor necrosis factor (TNF) alpha. Ridostin activated IFN alpha and suppressed TNF alpha and IFN gamma production by these cells. Monoclonal antibodies (MoAbs) to TNF alpha dose-dependently inhibited HIV-1 replication in these cells. Therefore it is possible that the observed anti-HIV activity of Ridostin in C8166 cells is partly mediated by altered cytokine production. Particularly, suppression of TNF alpha synthesis, that is known to activate HIV-1 replication in several model systems, can play a major role in the observed inhibition of HIV-1 replication.

Cell Line↗