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Biomedical subjects

A Bianco

Publications and source records attributed to A Bianco.

At least 55 records · Page 3Linked to original sources

Expression of intercellular adhesion molecule-1 (ICAM-1) in nasal epithelial cells of atopic subjects: a mechanism for increased rhinovirus infection?

Since clinical experimental studies indicate that upper respiratory tract viral infections may exacerbate acute asthma symptoms in atopic/asthmatic individuals, we have investigated the expression and modulation of ICAM-1 on human nasal epithelial cells (HNEC) from normal and atopic subjects. ICAM-1 is the attachment molecule for the majority of serotypes of human rhinovirus (HRV), including HRV-14, and is also critical for the migration and activation of immune effector cells. Basal ICAM-1 expression was significantly higher in HNEC obtained by brushings from atopic compared with non-atopic subjects (P = 0.031), and was also significantly increased on atopic HNEC harvested in season compared with out of season (P < 0.05). Atopic HNEC showed further up-regulation in ICAM-1 expression when cultured with clinically relevant allergen (P = 0.032). ICAM-1 levels on normal HNEC were also increased by infection with HRV-14 (P < 0.05). Basal expression of ICAM-1 on atopic nasal polyp epithelial cells (EC) was significantly higher than on both normal and atopic nasal HNEC. This elevated nasal polyp ICAM-1 level was not increased further by allergen, although HRV infection resulted in a small significant increase. Recovered viral titres from HRV-infected nasal polyp EC were 1.5-fold higher than from infected normal nasal HNEC. The data are consistent with the hypothesis that allergen, by enhancing expression of the HRV attachment target on host cells, facilitates viral infection in atopic subjects; simultaneously HRV-induced increases in ICAM-1 levels would favour migration and activation of immune effector cells to the airway, resulting in enhanced atopic inflammation.

Adult↗

Prevalence of hospital-acquired infections in Italy.

A one-day prevalence survey was conducted in Calabria (Italy) to estimate the prevalence of hospital-acquired infections (HAI) and the effect of different variables on HAI in 888 patients present in a ward for at least 24 hours and not due for discharge or transfer on the day of the survey. The overall prevalence of HAI was 1.7% and urinary tract and surgical wounds were the most frequent sites (each four patients, 26.7%). In only eight (53.3%) of the fifteen HAI detected, had a microbiological examination been requested and the only two positive culture results involved Pseudomonas aeruginosa (surgical site) and Escherichia coli (urinary tract). Results of multiple logistic regression analysis indicated that HAI differed significantly in prevalence between age groups, ward, and was higher in patients with urinary catheters and in those receiving antibiotics.

Adolescent↗

Polymorphism at the glutathione S-transferase GSTP1 locus. A new marker for bronchial hyperresponsiveness and asthma.

Most genetic studies of asthma have concentrated on genes on chromosomes 11q and 5q and their association with the key asthma-related phenotypes of bronchial hyperresponsiveness (BHR) and atopy. Although asthma is characterized by airway inflammation, a critical component of which is oxidative stress, few data exist on genes involved in protecting against this insult. We describe an association study designed to examine whether allelic variation at the glutathione-S-transferase GSTP1 locus influences expression of the BHR and atopy phenotypes in asthma. The enzyme encoded by GSTP1 utilizes a variety of lipid and DNA products of oxidative stress, and polymorphic variants of this gene are associated with altered catalytic function of this enzyme. We found that the frequency of GSTP1 Val(105)/Val(105) was significantly lower in asthmatic than in control subjects. Indeed, the presence of this genotype conferred a sixfold lower risk of asthma than did GSTP1 Ile(105)/Ile(105). Remarkably, asthma risk in Val(105) homozygotes was further reduced (by ninefold) after correction for atopic indices, age, and gender. Trend analysis after stratification according to the degree of bronchial reactivity/obstruction showed that the frequency of GSTP1 Val(105)/Val(105) correlates with decreasing severity of airway dysfunction. Furthermore, subjects with GSTP1 Val(105)/Val(105) have four- and 10-fold lower risks, respectively, of exhibiting atopy defined by skin test positivity and IgE level. These data show that GSTP1 polymorphism is strongly associated with asthma and related phenotypes, and provide an alternative explanation for the linkage of chromosome 11q13 with BHR and atopy.

Adult↗

Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate whether the addition of gemcitabine (G) to vinorelbine (V) improves survival and quality of life (QoL) among elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC aged >/= 70 years with advanced disease were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1,200 mg/m(2) + V 30 mg/m(2) on days 1 and 8 every 3 weeks. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned based on the first 60 patients per arm. RESULTS: In May 1999, the survival data were analyzed of 120 eligible patients (V group = 60; G + V group = 60) who had been randomized from June 1997 to February 1999. Forty-nine patients had stage IIIB disease, and 71 had stage IV. At a median potential follow-up of 14 months (range, 3 to 22 months), 93 patients had died (G + V group = 41; V group = 52). In the G + V group, median survival time was 29 weeks and projected 1-year survival was 30%; these values were 18 weeks and 13% in the V group. According to multivariate Cox analysis, the risk of death in the G + V arm compared with the V arm was 0.48 (95% confidence interval, 0. 29 to 0.79; P <.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The overall response rates were 22% and 15% in the G + V and V groups, respectively. CONCLUSION: In elderly patients with NSCLC, G + V treatment is associated with significantly better survival than is V alone.

Aged↗

Food handlers and foodborne diseases: knowledge, attitudes, and reported behavior in Italy.

The purpose of this study was to evaluate knowledge, attitudes, and behavior concerning foodborne diseases and food safety issues among food handlers in Italy. Face-to-face interviews were conducted within a random sample using a structured questionnaire. Of the 411 food handlers responding, 48.7% knew the main foodborne pathogens (Salmonella spp., Staphylococcus aureus, Vibrio cholerae or other Vibrio spp., Clostridium botulinum, hepatitis A virus), and this knowledge was significantly greater among those with a higher education level, in practice from a longer period of time, and who had attended education courses (P < 0.05). A vast majority (90.4%) correctly indicated those foods classified as common vehicles for foodborne diseases, and only 7.1% of food handlers were able to name five different food vehicles, each of which transmit one of the five pathogens. The proportion of those who were able to specify a food vehicle that transmitted hepatitis A virus was significantly higher for those with a higher educational level and with a longer food-handling activity. A positive attitude toward foodborne diseases control and preventive measures was reported by the great majority of food handlers, and it was more likely achieved by those who had attended education courses. This attitude was not supported by some of the self-reported safe practices observed for hygienic principles, because only 20.8% used gloves when touching unwrapped raw food, and predictors of their use were educational level and attending education courses. Results strongly emphasize the need for educational programs for improving knowledge and control foodborne diseases.

Adolescent↗

Appropriateness of hospital utilisation in Italy.

The purpose of this study was to determine the extent of inappropriate hospital admission and inappropriate days of stay and the effect of variables on such inappropriateness on an adult population in Italy. A review was made of medical records of patients admitted to any one of the following specialities: medicine, surgery, gynaecology or traumatology/orthopaedics at one of five hospitals located respectively in Siena, Frosinone, Rome and Catanzaro, and who were in-patients during one of four pre-selected index days. To determine the appropriateness of hospital admission and length of hospitalisation, a retrospective application was made using the Italian version of Appropriateness Evaluation Protocol (AEP). A total of 1299 patient days were reviewed. 14.2% of the hospital admissions and 37.3% of the number of hospitalisation days were judged to be inappropriate. Multiple logistic regression analysis showed that inappropriate admission was significantly increased with relation to: greater distance from hospital to patient's home; admission to a medical ward; planned admissions; and admission over a weekend. Multiple logistic regression analysis indicated that the inappropriate number of days of hospitalisation was significantly higher for medicine and for patients who were inappropriately admitted. The main reason for categorising an admission as inappropriate was that the patient's problems could be treated on an out-patient basis, and, for inappropriate days of care, the physician was overtly cautious in the management of a patient. Changing the physicians' behaviour and the organisation of hospital activities may be effective in improving the quality and efficiency of hospital care.

Adolescent↗

Cutting edge: N-hydroxy peptides: a new class of TCR antagonists.

TCR antagonists are altered T cell epitopes that specifically inactivate T cells. Commonly, they are derived from agonists by amino acid side chain replacement at positions accessible to the TCR. In this paper we report for the first time that a main chain N-hydroxylation, which is not exposed at the surface of the MHC peptide complex, renders an agonist into an antagonist. These mimotopes are a new, yet undescribed class of TCR antagonists. The antagonists are about 100 times more potent than an unrelated peptide that competes for binding to the MHC molecule. The novel main chain modification enhances biostability and maintains side chain constitution and thus opens new prospects for the use of TCR antagonists in the treatment of pathological immune reactions.

Animals↗

Breast and cervical cancer screening: knowledge, attitudes and behavior among schoolteachers in Italy.

The study explores knowledge, attitudes and behavior regarding screening for breast and cervical cancers. All female teachers in primary and secondary schools in Crotone and in Cassino (Italy) received a questionnaire on demographic and socioeconomic characteristics, clinical history, knowledge, behavior and attitudes about breast and cervical cancer and related screening procedures. A response rate of 65% was achieved. Knowledge on effectiveness of mammography and pap test in finding related cancers was widely spread in the sample. Only about 30% and 50% had respectively undergone their last mammogram and pap test according to the recommended time interval. Having been examined by a physician in the previous year and having had a screening CBE or a screening pap smear in the past three years were significantly more likely in women who underwent mammography for screening purposes in the past two years. Pap smear in the previous three years was significantly more likely in women in their forties, with a higher family income and in those who had been examined by a physician in the previous year. The results strongly recommend continued emphasis of physicians on education of women regarding mammography and pap smear.

Adult↗

N-hydroxy peptides as substrates for alpha-chymotrypsin.

An N-hydroxylated peptide bond was found to be cleaved faster by an endopeptidase than the corresponding peptide bond. This preferred enzymatic cleavage was detected during proteolytic studies of the N-hydroxy peptide SIINFpsi[CO-N(OH)]GKL in the presence of the serine protease alpha-chymotrypsin in comparison with the natural SIINFEKL epitope and related analogs. For the first time, the replacement of the peptide bond by another motif afforded an oligomer which is degraded faster than the natural peptide. The N-hydroxy peptide is also more sensitive to the enzymatic degradation than the Gly-containing analog SIINFGKL. A tentative explanation for the unexpected higher cleavage rate of the CO-N(OH) bond is given on the basis of the N-OH intramolecular H-bonding capacity as indicated by NMR experiments. This property of the hydroxamate group may be of particular advantage for the introduction of a specific cleavage site within peptidomimetics or in prodrugs.

Amino Acid Sequence↗

Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group.

PURPOSE: In a previous phase I study cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR) combination therapy was safe and very active in patients with non-small-cell lung cancer (NSCLC). This study was aimed at better defining the activity and toxicity of this regimen. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients, age < or = 70 years, with stage IIIB or IV NSCLC and a performance status of 0 or 1 (Eastern Cooperative Oncology Group scale) were randomized to two treatment arms. Patients on arm A received CDDP 50 mg/m2, GEM 1,000 mg/m2, and VNR 25 mg/m2 on days 1 and 8 of an every-3-weeks cycle (57 patients). Patients on arm B received CDDP 80 mg/m2, epirubicin 80 mg/m2, and vindesine 3 mg/m2, all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients). In December 1996, randomization was stopped early, and an additional 30 patients were treated with the experimental regimen to obtain a more accurate estimation of its activity rate. RESULTS: Among 87 patients who received the CDDP-GEM-VNR combination, four complete responses (CRs) and 46 partial responses (PRs) were observed, for an overall response rate of 57% (95% confidence interval [CI], 46% to 68%). Two CRs and 18 PRs were recorded among 54 patients on arm B, giving a 37% activity rate (95% CI , 24% to 51%). After a median follow-up duration of 19 months, the median progression-free and overall survival durations were 32 and 50 weeks in arm A, and 18 and 33 weeks in arm B, respectively. World Health Organization grade 3 to 4 neutropenia and thrombocytopenia occurred in 46% and 14% of patients in arm A and in 22% and 11% of those in arm B, respectively. Severe nonhematologic toxicity was uncommon in both arms. CONCLUSION: The CDDP-GEM-VNR combination is a highly effective treatment for patients with advanced NSCLC and has a manageable toxicity. A phase III trial comparing this new combination with both CDDP-VNR and CDDP-GEM regimens is underway.

Adult↗

Measurement of the amniotic fluid index with and without color Doppler.

AIMS: The purpose of this study was to assess the effect, if any, of color Doppler on the measurement of the amniotic fluid index in term pregnancies. It is hypothesized that color Doppler may enhance the detection of oligohydramnios. METHODS: The amniotic fluid index was performed with and without color Doppler on pregnancies greater than or equal to 36 weeks gestational age. Differences in the mean amniotic fluid index measurements were assessed. The incidence of oligohydramnios was examined using both techniques. Differences in continuous variables were assessed with the paired t test, differences in categorical variables were assessed using the Fisher Exact Test. RESULTS: There were 155 pregnancies examined, the amniotic fluid index was significantly decreased when color Doppler was added to the standard technique. (P < .0001) The incidence of oligohydramnios was higher with the application of color Doppler to the standard amniotic fluid index. (P < .05). CONCLUSIONS: Color Doppler results in a significantly lower amniotic fluid volume measurement and may enhance the detection of oligohydramnios.

Adult↗

Comparison of delayed absorbable suture v nonabsorbable suture for treatment of incompetent cervix.

UNLABELLED: This is a retrospective study of McDonald cerclages comparing absorbable suture v. nonabsorbable suture and showing no adverse outcomes associated with the absorbable cerclage group. OBJECTIVE: To compare the efficacy of traditional nonabsorbable suture to delayed absorbable suture for use in McDonald cervical cerclage. STUDY DESIGN: A retrospective analysis was conducted examining all cerclage procedures over a one year interval, from 7/01/97 until 6/03/98. Cases were stratified by the type of suture material, specifically nonabsorbable versus delayed absorbable. Demographic data, as well as selected perinatal outcomes were analyzed for each group. Statistical analysis was performed using Chi-square and Fishers Exact test for categorical data, and the Student t-test for continuous variables. A p < .05 was considered statistically significant. RESULTS: Eighteen patients who underwent a McDonald cerclage were analyzed. In fourteen a nonabsorbable cerclage was utilized and in four an absorbable cerclage was used. The mean gestational age at delivery for the nonabsorbable suture group was 36.9 weeks compared to 39.2 weeks for the patients receiving an absorbable cerclage (P = 0.2). The mean birth weights for each group were 2732 +/- 183 grams and 3616 +/- 343 grams, respectively (P = 0.04). CONCLUSION: Based on our findings delayed absorbable suture material may be a reasonable alternative during cerclage placement, with the added benefit of spontaneous degradation versus surgical removal.

Absorption↗

New synthetic non-peptide ligands for classical major histocompatibility complex class I molecules.

Poly-N-acylated amines, as a new class of synthetic non-peptide ligands for the murine major histocompatibility complex (MHC) class I molecule H-2Kb, were developed on the basis of the ovalbumin-derived peptide epitope SIINFEKL. Non-peptidic structural elements were introduced at the C-terminal part of the ligand and include the two dominant anchors at positions 5 and 8. Several oligomers and five different combinatorial libraries were synthesized and tested for their H-2Kb-binding capacities in an MHC stabilization assay. First, the optimal spacing and geometry of the side chains were determined using a series of oligomers with different main chain modifications. Then, based on the structure with the highest binding efficiency, randomized libraries were designed that contain 26 different aromatic, heteroaromatic, or pseudoaromatic side chains for the dominant anchor at position 5, which is deeply buried inside the MHC peptide-binding groove and is crucial for the conformational stability of the entire peptide-MHC complex. Similarly, a series of aliphatic side chains were tested for the second dominant anchor at position 8. MHC-binding and MHC-stabilizing oligomers with defined structures were derived from these libraries by deconvolution.

Amines↗

Trans-cis amide bond isomerization in fulleroprolines.

The 1H NMR study of fulleroproline derivative Ac-Fpr-OtBu and its Pro analogue Ac-L-Pro-OtBu over a range of temperatures in toluene-d8 solution has enabled the comparison of their equilibrium and activation parameters for the trans/cis interconversion around the amide partial double bond.

Bacterial Proteins↗

N-Hydroxy-amide analogues of MHC-class I peptide ligands with nanomolar binding affinities.

A novel class of major histocompatibility complex class I (MHC-I) ligands containing an N-hydroxyamide bond was designed on the basis of the natural epitope SIINFEKL, and synthesized on solid phase. The capacity of these compounds to bind to the MHC-I molecule H-2Kb and to induce T cell responses was analysed in comparison with the corresponding glycine containing variant of SIINFEKL. Binding to the MHC molecule was diminished by the N-hydroxy group at positions 2 and 3 of the oligomer and improved in the case of positions 4, 5, 6 and 7. No change was seen for position 1. The efficacy of T cell stimulation was strongly reduced by the modification of all positions except for position 1. A complete loss of activity was found for the N-hydroxy variant in positions 4 and 6. N-Hydroxy amide-containing peptides displayed an enhanced stability to enzymatic degradation. This new class of MHC ligand can become instrumental as immunomodulatory reagent in various disease situations.

Amides↗

Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1.

Intercellular adhesion molecule (ICAM)-1 is a cell receptor important in both human rhinovirus (HRV) attachment and immune effector cell mobilization. The level of expression of ICAM-1 by epithelial cells (EC) therefore plays a crucial role in the intricate biological phenomena underlying viral binding, host infection and consequent inflammatory events. As T-helper (Th)2 lymphocytes predominate within the asthmatic airway, the influence was evaluated of Th2-associated mediators in the modulation of ICAM-1 expression on uninfected and HRV-infected EC. H292 EC were cultured in vitro, with varying concentrations of interleukin (IL)-4, IL-5, IL-10 and IL-13 for 24 h and then infected with live HRV-14. Surface ICAM-1 expression was assessed by immunocytochemistry. Infection with HRV-14 resulted in a twofold increase in ICAM-1 expression. IL-4, IL-5, IL-10 and IL-13 produced a 2.7-5.1-fold enhancement of ICAM-1 expression of uninfected cells and caused approximately a further twofold increase in infected cells over the expression induced by HRV infection itself. Interferon-gamma in combination with each Th2-associated cytokine only slightly reduced, but did not override, the Th2-induced level of ICAM-1 expression on both uninfected and virus-infected EC. These data suggest that the effects of Th2-associated cytokines on intercellular adhesion molecule-1 expression and recovery of infectious virus are dominant over the effects of the Th1-associated cytokines such as interferon-gamma. Since the airway mucosa in atopic asthma is predominantly infiltrated by Th2 lymphocytes, these results could explain both the increased susceptibility to human rhinovirus infection in asthmatic patients and the associated exacerbation of asthma symptoms.

Cells, Cultured↗

A biological model to explain the association between human rhinovirus respiratory infections and bronchial asthma.

Human rhinoviruses (HRVs) are a frequent cause or upper respiratory tract infections in children and adults, and can exacerbate existing pulmonary disease. The major group of HRV attach to the receptor intercellular adhesion molecule (ICAM)-1, which is expressed on many cell types including epithelial cells. To study the influence of biological mediators on ICAM-1 expression, and consequently HRV attachment and infection, we have established an in vitro model system to evaluate the effects or pre-exposure to different cytokines on surface expression of ICAM-1 of uninfected and HRV-14-infected epithelial cells. The results of our studies show that the cytokines interleukin (IL)-1 beta, IL-8 and tumour necrosing factor (TNF)alpha increased ICAM-1 expression on epithelial cells. Epithelial cells infected with live HRV-14 displayed a significant upregulation of ICAM-1 compared to baseline. In contrast, interferon (IFN)gamma, whilst increasing the level of ICAM-1 expression on uninfected cells, induced a marked persistent downregulation of ICAM-1 expression on HRV-infected epithelial cells. In addition, IFN gamma appeared to completely override the ICAM-1 upregulation induced by IL-1 beta, IL-8 and TNF alpha, during HRV infection. We have further demonstrated that type 2 T-helper cell (Th2)-associated cytokines, predominantly IL-13, induce a marked upregulation or epithelial cell surface ICAM-1, thus increasing cellular binding sites for HRV attachment. As the airway mucosa or asthmatic subjects is predominantly infiltrated by activated type 2 T-helper cells with a simultaneous decrease of type 1 T-helper cells, our observations could explain the increased susceptibility to human rhinovirus infection observed in asthma.

Adult↗