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Biomedical subjects

C Mancini

Publications and source records attributed to C Mancini.

At least 55 records · Page 3Linked to original sources

Characterisation and protective capacity of monoclonal antibodies elicited in mice against protein epitopes of antibiotic-exposed Escherichia coli.

The binding capacity and the protective activity of three monoclonal antibodies (MAbs)-ARM 1-4, ARM 1-7 and ARM 2-2-obtained from spleen cells of mice immunised with Escherichia coli O6:K-pre-treated with sub-MIC of aztreonam were studied. The MAbs belonged to IgG1 isotype and showed different reactivity toward protein epitopes of E. coli in an immunoblotting assay. ARM 1-4 recognised epitopes on molecules of 30 kDa and 40 kDa. ARM 1-7 identified an epitope of a molecule of 41 kDa, and ARM 2-2 recognised epitopes of molecules of 15 kDa and 41 kDa. In ELISA the MAbs cross-reacted with E. coli O7:K-, E. coli O111:B4 and E. coli O128:K- with different binding affinity. Furthermore, the MAbs showed complement-dependent bactericidal activity. The MAbs displayed different protective capacities when given to mice 90 min before lethal challenges with 2 x LD50, 4 x LD50 and 8 x LD50 of E. coli strains. In all but one instance (ARM 1-4 versus E. coli O7:K-) it was not possible to correlate protective capacity with binding affinity of a MAb to a given bacterial cell. Therefore, the epitopes recognised by the MAb may be more closely associated with bacterial virulence than in binding to the bacterial cell.

Animals↗

The release of tumor necrosis factor alpha (TNF-alpha) by interferon gamma (IFN-gamma) induced THP-1 cells stimulated with smooth lipopolysaccharide is inhibited by MAbs against HLA-DR and CD14 receptors on the effector cell.

Bacterial lipopolysaccharide (LPS) plays a central role in the pathogenesis of gram-negative sepsis and shock. The glycosylphoshatidyl inositol (GPI) anchored glycoprotein CD14 on mononuclear cells binds LPS, especially in the presence of an LPS binding serum protein, activating the production of pro-inflammatory cytokines, i.e. TNF-alpha. However, since GPI anchorage to the cell membrane lacks the intracellular signalling capacity, the existence of at least a second receptor has been postulated. In attempt to identify additional LPS receptors, we used the human myelomonocytic cell line THP-1. This undifferentiated cell line did not respond to LPS in terms of TNF-alpha release, but when induced with 250 U/ml of IFN-gamma for 48 h, the cells released TNF-alpha (174 +/- 58.6 U/ml. L929 cell bioassay) in response to 10 vg/ml of E. coli 0111 LPS, in the absence of serum. Blockade of either HLA-DR or CD14 receptors with specific MAbs did not reduce the amount of cytokine released. However, when both the receptors were sequentially blocked involved on the effector cells a remarkable inhibition of TNF-alpha release was observed (8.6 +/- 1.4). It seems therefore, that HLA-DR receptor may be with CD14 in triggering TNF-alpha release by IFN-gamma, induced THP-1 cells.

Antibodies, Monoclonal↗

Buspirone augmentation of selective serotonin reuptake inhibitors (SSRIs) in social phobia.

We evaluated the efficacy of buspirone, in the augmentation of social phobic symptom response to the selective serotonin reuptake inhibitors (SSRIs). Ten patients meeting DSM-III-R criteria for generalized social phobia were studied. Patients obtaining only a partial response to an adequate trial of an SSRI, received buspirone in addition to the SSRI for 8 weeks in an open trial. Seven patients (70%) were considered responders (moderate or marked improvement) and 3 (30%) were considered nonresponders (minimal improvement or no change). This study provides clinical evidence suggesting that buspirone augmentation may be a useful clinical strategy in social phobic patients who show a partial response to an SSRI.

Adolescent↗

A high-risk pilot study of the children of adults with social phobia.

OBJECTIVE: Children of patients with social phobia were studied to estimate their rates of psychiatric disorder. METHOD: Twenty-six social-phobic outpatients who had at least one child between the ages of 4 and 18 years participated in the study. Information was collected from parents on all 47 children and from the children between 12 and 18 years of age. Diagnoses in the children were made based on DSM-III-R and were done by a best-estimate method, using parent and child reports from a modified Anxiety Disorders Interview Schedule for Children, the Survey Diagnostic Instrument, the Current Self-Report Childhood Inhibition Scale, and the Alcohol Dependence Survey. RESULTS: Of the 47 children, 49% had at least one lifetime anxiety disorder diagnosis. The most common diagnoses were overanxious disorder (30%), social phobia (23%), and separation anxiety disorder (19%). Sixty-five percent had more than one anxiety disorder diagnosis. Lifetime major depression was found, in 8.5% of the children. Parents whose children met criteria for an anxiety disorder had a greater mean number of comorbid diagnoses than did the parents of unaffected children. CONCLUSION: This pilot study suggests that children of social-phobic parents may have increased rates of psychiatric disorder. Further studies incorporating a control group are needed.

Adolescent↗

Paroxetine in social phobia.

BACKGROUND: Several open trials suggest the efficacy of the selective serotonin reuptake inhibitors (SSRIs) in social phobia. This study attempted to assess the efficacy of paroxetine, a new SSRI, in the treatment of social phobia. METHOD: Paroxetine was administered to 18 patients who had a primary DSM-III-R diagnosis of social phobia, generalized type (diagnosed by using the Structured Clinical Interview for DSM-III-R), in a 12-week open, clinical trial. Treatment began at 10 mg of paroxetine daily and was increased according to clinical response and side effects. Patients completed self-report measures at baseline and at Weeks 4, 8, and 12. These measures included the Fear of Negative Evaluation Scale, the Social Avoidance and Distress Scale, the Social Anxiety Thoughts Questionnaire, the Fear Questionnaire, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Social Adjustment Scale Self-Report, and the Sheehan Disability Scale. Clinicians completed the Liebowitz Panic and Social Phobic Disorders Rating Form. RESULTS: All 18 patients completed the 12-week trial. Fifteen (83.3%) were considered responders (moderate or marked improvement), and 3 (16.7%) were considered to be nonresponders (minimal improvement or no change of their symptoms). All measures of social anxiety, social phobic avoidance, depression, and social functioning showed a statistically significant change at endpoint. CONCLUSION: These findings support a role for paroxetine in the treatment of social phobia, generalized type. Controlled studies will be required to further investigate this preliminary finding as well as to compare paroxetine with other pharmacologic treatments of social phobia.

Adolescent↗

Bronchial epithelial cells of atopic patients with asthma lack the ability to inactivate allergens.

The cause of asthma is still unknown. Though most asthmatic patients are atopic, only certain atopic subjects develop this disease, and atopic asthmatics recover from asthma after transplantation of lungs from nonasthmatic donors. Thus, there might be a primary local defect in the bronchial wall which affects the expression of asthma in atopic individuals. We show here that the bronchial epithelial cells from atopic patients with asthma are aberrantly permeable to the airborne allergen most often implicated in the pathogenesis of this disease, indicating how it can have access to the antigen-presenting cells (dendritic cells) below the apical surface of the epithelium in vivo. In addition, allergen exposure induces asthmatic epithelial cells to express granulocyte/macrophage colony-stimulating factor, a cytokine involved in the proliferation and function of dendritic cells.

Allergens↗

Optimization and comparison of three different methods for the determination of Rn-222 in water.

Three different systems for the determination of radon in water have been examined: liquid scintillation counting (LSC), degassification followed by Lucas cell counting (LCC) and gamma counting (GC). Particular care has been devoted to the sampling methodologies of the water. Comparative results for several environmental samples are given. A critical evaluation is also given on the basis of the final aim of the measurements.

Radon↗

Differential effects of gonadectomy on thymic stromal cells in promoting T cell differentiation in mice.

Twenty-six week-old BDF1 mice were gonadectomized and grafted with thymus from irradiated (8.5 Gy) newborn, 6-week-old, or 26-week-old mice. One month later, grafted thymuses were recovered and examined in terms of thymocyte numbers, subpopulations and proliferative responses to Concananavlin A (Con A). The growth of the irradiated thymus was significantly higher in gonadectomized (Gx) than in sham-operated (Sham) mice and the magnitude of thymic growth was apparently age-dependent, as it was greater for newborns than for older mice. Con A response of thymocytes was also significantly higher in Gx mice than in Sham mice, and the magnitude of the response declined with advancing age of the thymus donors. Flow cytometric analysis revealed that a significant increase in the percentage of CD4+CD8- was observed in thymus grafts showing high Con A responses. However, this effect of Gx on the thymus graft was dependent on age of the thymus donor. Namely, newborn thymus grafts could grow equally well in both Gx and Sham recipients, whereas thymus grafts from 6- and 26-week-old mice could grow well only in Gx, but not in Sham recipients. The number of thymocytes was comparable in thymus grafts from 6- and 26-week-old mice, but the proliferative response to Con A was higher in the former than in the latter graft. Collectively, Gx appeared to promote immigration of thymocyte precursors into the thymus and to enhance proliferation and differentiation of thymocytes towards CD4+CD8- T cells, in an age-related manner.

Aging↗

IgM anti-hepatitis C virus in patients with chronic non-A, non-B hepatitis and their relationship to viral replication.

Patients with hepatitis C virus (HCV) infection may have different patterns of antibody response to various structural and non-structural viral antigens. We have correlated the serological patterns to the clinical features of chronic infection and to viral replication in 68 HCV-Ab-positive patients with chronic liver disease at different stages (19 with cirrhosis-hepatocellular carcinoma, 38 with chronic active hepatitis and 11 with chronic persistent hepatitis). Serum samples from each patient were assayed for HCV-IgM by enzyme immunoassay and for HCV-RNA by the polymerase chain reaction using primer sets derived from the 5'-non-coding region. The prevalence of HCV-IgM was high (54 patients (79.4%)) and the study showed a good correlation between high values of anti-HCV-IgM and the presence of HCV-RNA in serum, since HCV-RNA was detected in 35 of the 54 IgM-positive patients (64.8%) and notably in 19 of the 20 subjects with high levels of specific IgM. Conversely, all the 35 sera containing HCV-RNA were also reactive for HCV-IgM, while none of the HCV-IgM-negative sera was HCV-RNA reactive. Positivity rates for both HCV-RNA and IgM anti-HCV were higher in the more advanced stages of disease; thus, the clinical pattern of HCV chronic hepatitis seems to be strictly related to the serological pattern and the presence of HCV-RNA.

Journal Article↗

Determination of waterborne 222Rn concentrations using AC canisters.

A method for measuring 222Rn concentration in water using charcoal canisters is presented. 222Rn is transferred within a few minutes from water contained in a 0.720 L bottle to a charcoal canister using a portable degassing unit. In the laboratory, gamma counting is performed at least 10 h after sampling to determine waterborne 222Rn concentration. The results obtained with charcoal canisters are compared to measurements made with Marinelli beakers calibrated in a comparison with liquid scintillation counting. The efficiency of transferring dissolved 222Rn in water to activated charcoal is 99%, based on measurements made using Marinelli beakers. The lower limit of detection at the 95% confidence level is approximately 1 kBq m-3 for a 15 min gamma count. The system was used to measure radon concentration in mineral groundwater near Rome.

Radon↗

Relationship of childhood sexual and physical abuse to anxiety disorders.

This study reports on the relationship of childhood sexual and physical abuse in adult outpatients of an anxiety disorders clinic. A total of 205 consecutive patients admitted to two anxiety disorders clinics in Hamilton, Ontario, Canada, were given the Child Maltreatment History-Self-Report to elicit a history of childhood sexual or physical abuse. Childhood sexual abuse was reported by 23.4% and childhood physical abuse by 44.9%. Patients with a history of childhood sexual or physical abuse had significantly higher Beck depression scores and concurrent major depression, as well as more significant impairment in social functioning. They also demonstrated significantly higher state and trait anxiety scores. The occurrence of sexual or physical abuse was not associated with the presence of any particular primary anxiety disorder diagnosis. However, childhood sexual and/or physical abuse may affect the severity of the anxiety disorder as well as the presence of concurrent major depression.

Adult↗

Evaluation of efficacy and safety of erdosteine in patients affected by chronic bronchitis during an infective exacerbation phase and receiving amoxycillin as basic treatment (ECOBES, European Chronic Obstructive Bronchitis Erdosteine Study).

An international multicentric study was conducted with the aim of demonstrating that erdosteine improves the efficacy of amoxycillin in the treatment of infective exacerbation of chronic bronchitis mainly on the clinical symptomatology (primary objective), on spirometric tests and body temperature, without negatively influencing the tolerance (secondary objectives). The study was conducted as a prospective evaluation, with 2 comparative groups treated with erdosteine (300 mg x 2/day) or placebo in association with amoxycillin (1500 mg/day) for a maximum of 10 days. The design of the trial was double-blind and parallel group with 2 subgroups. The treatments have been assigned randomly to a population of chronic bronchitic patients in exacerbation phase of n = 237 subjects. The study was conducted according to the principles of the Declaration of Helsinki and its amendments (Hong Kong, September 1989). The primary end-point used to determine effectiveness in this study was the global clinical assessment (GCA) which was choosen as a general indication of activity with objective/subjective evaluation of the clinical picture. Secondary endpoints of efficacy are sputum parameters, functional signs of chronic obstructive bronchitis, spirometric tests and overall judgement of efficacy. Safety was evaluated with adverse drug reactions reporting, arterial blood pressure, heart rate and laboratory tests monitoring. The obtained values have been analyzed with two-way and factorial ANOVA, Least Squares Catmod-SAS, Wilcoxon and Chi-square tests. The number of patients included in the effectiveness analysis is of n = 226 subjects, due to the fact that 11 patients were lost due to different reasons. In term of results as far as the primary objective of the study was concerned, erdosteine resulted more active than placebo. The analysis evidenced a very significant difference for treatment, time and interaction time x treatment. No difference on the contrary was observed for center and the interaction center x treatment. Sputum volume, body temperature and spirometric parameters were not significantly influenced by both treatments. Viscosity, appearance as well as functional signs evidenced a modification over time in favour of erdosteine. As safety is concerned the majority of adverse events, both in the erdosteine and in the placebo group, were related to the gastrointestinal area. For erdosteine, of 9/17 side-effects, 3 were epigastralgias, 3 nauseas, 1 diarrhoea, 1 taste loss, 1 hemorrhoids. For placebo of 13/17 related events 3 were epigastralgias, 4 nauseas, 4 diarrhoeas, 1 pyrosis, 1 dry mouth. In terms of severity they have been all defined as mild or moderate degree. Also from a qualitative perspective it is clear that there are no relevant differences between the 2 treatments under evaluation, concerning safety. In conclusion of particular interest is the datum arising from the efficacy/safety evaluation, which indicates that the clinical picture is modified earlier and at deeper degree by the synergistic activity of erdosteine and of the antibiotic without the risk of an augmentation of side-effects incidence.

Aged↗

Evaluation of indeterminate sera for hepatitis C virus by assays using synthetic peptides.

The development of new immunodiagnostic systems to study antibodies anti-HCV based on the use of synthetic peptides are potentially very important in the evaluation of indeterminate samples. We have compared two immunodiagnostic tests, the 3-RIBA and LIA-HCV test system, to examine the samples rated as indeterminate by the 2-RIBA test. The results showed that the specificity of the new tests has improved, in fact 29/40 of the indeterminate samples studied became positive with both tests. However, the 3-RIBA test showed higher sensitivity, since two samples negative by LIA-HCV, were positive with this system.

Enzyme-Linked Immunosorbent Assay↗

Sertraline in social phobia.

Twenty-two patients meeting a primary DSM-III-R diagnosis of Social Phobia, entered a 12 week open trial of sertraline. Twenty patients completed at least 8 weeks of treatment. Sixteen patients (80%) were considered responders and 4 (20%) were considered non-responders. All measures of social anxiety and avoidance, depression and social functioning showed a statistically significant change from baseline to end point.

Adolescent↗

Murine monoclonal antibody elicited with antibiotic-exposed Escherichia coli exerts protective capacity in experimental bacterial infections.

Escherichia coli pre-exposed to a sub-minimal inhibitory concentration (sub-MIC) of several antibiotics elicits an enhanced humoral response which is protective against challenges with untreated homologous and heterologous bacteria. To characterise the specificity of this response we produced murine monoclonal antibodies (MAbs) to aztreonam-treated E. coli O6:K-. This resulted in the identification of MAb MT 1F, of isotype IgG1, that recognised a 12-kDa protein component of the untreated bacterial cells. After passive transfer, the MAb displayed protective activity in mice infected with lethal doses of live E. coli O6:K- and E. coli O111:B4. In ELISA experiments the MAb cross-reacted with structures located on whole cells of E. coli O6:K-, E. coli O111:B4, E. coli J5 and Salmonella minnesota Re595 and it also exerted a bactericidal activity against live E. coli O6:K-. The modifications induced by antibiotic treatment may unmask bacterial epitopes that may elicit the production of MAbs endowed with protective capacity.

Animals↗

[The evolution of serologic tests in the diagnosis of HCV infections].

The Authors take in account the technical aspects of the serological tests for the diagnosis of HCV infections. Particularly they consider the better diagnostic capacity of the 2nd generation and, at the present time, 3rd generation screening tests compared to tests of 1st generation. This happens because an antigen, the c33-c, codified by a genomic sequence, specific for the non-structural proteins, NS3, of the genome of HCV virus is used in the last methodologies. This antigen induces the production of specific antibodies more quickly than the other antigenic proteins. Moreover in many cases of HCV infections it has been evidenced that the anti-c33-c are the only antibodies produced. For this reason the tests that use this antigen not only allow an early diagnosis, enclosing the "window effect", but in every case have the best diagnostic capacity. Moreover the authors evaluate also the tests defined "confirmatory tests", in which the importance of the presence of systems for the identification of both anti-c33-c and c22-3 antibodies is evidenced.

Antigens, Viral↗

Leukotrienes and alpha tumor necrosis factor levels in the bronchoalveolar lavage fluid of patient at risk for the adult respiratory distress syndrome.

OBJECTIVE: To examine bronchoalveolar lavage (BAL) fluid of patients at risk for Adult Respiratory Distress Syndrome in the attempt to provide evidence of an increased local production of Leukotrienes (LTS) and Tumor Necrosis Factor (TNF). DESIGN: Prospective, comparative, clinical study. SETTING: ICU in a university hospital. PATIENTS: 14 patients at risk for ARDS and 10 control patients undergoing mechanical ventilation, were studied. INTERVENTION: BAL was performed in each patient at the time admission to the ICU (T0), and after 48 hours (T1). RESULTS: Our controls never showed levels of TNF > 10 pg/ml and their LTS amounts were always below the detection limit. All patients at risk had levels of TNF ranging between 22 and 130 pg/ml, but no difference was noticed between patients who developed ARDS and those who did not, between survivors and non survivors, and between septic and non septic patients. LTD4 and LTB4 (ranging between 30 to 1365 pg/ml) were detected only in six of the 14 patients. Among these 6 patients, 4 developed ARDS. In these patients we could correlate LTB4 with TNF levels and the number of neutrophils recovered from the BAL fluid. CONCLUSION: In our patients leukotrienes and TNF in the BAL fluid correlate well with the acute inflammatory phase of ARDS, as reflected by the increase number of leukocytes in the fluid retrieved, but they do not appear to be clearly predictive index for the syndrome.

Adult↗