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Biomedical subjects

A Sanduzzi

Publications and source records attributed to A Sanduzzi.

At least 19 recordsLinked to original sources
PubMed2005

Role of mycobacteria-induced monocyte/macrophage apoptosis in the pathogenesis of human tuberculosis.

Apoptosis is a physiological programmed cell death process whose dysregulation plays an important role in different human infectious diseases. An increasing number of intracellular pathogens are known to induce target cell apoptosis, while some other parasites inhibit it. Unlike necrosis, apoptosis is a silent immunological event occurring without inflammation. Infection-induced target cell apoptosis may be a successful strategy to eliminate pathogens and assure host survival. Conversely, apoptosis inhibition could represent an adaptive mechanism for pathogen survival, while it may be beneficial for the host to initiate an effective immune response. The worldwide increase in tuberculosis has stimulated more research aimed at defining the interaction between Mycobacterium tuberculosis and the immune system. M. tuberculosis possesses sophisticated strategies to circumvent its fate within target monocytic cells. Apoptosis of alveolar macrophages and monocytes has been described as a consequence of M. tuberculosis infection. Moreover, the observation that mycobacterial lipoproteins activate macrophages through Toll-like receptor (TLR) 2 suggests that innate immune receptors contribute to defence against M. tuberculosis. There is evidence that TLR-induced apoptosis modulates inflammation and immune activation during M. tuberculosis infection. Finally, the role of apoptotic-infected cells as a source of microbial antigens for cross-priming of effector T-cells is also discussed.

Apoptosis↗
PubMed2003

T lymphocyte phenotypic profile in lung segments affected by cavitary and non-cavitary tuberculosis.

Clinical manifestations of pulmonary tuberculosis (TB) may depend on a complex interaction between the host and the pathogen. Clinical outcomes of pulmonary tuberculosis are variable, ranging from asymptomatic lifelong infection to parenchymal lung destruction, resulting in cavitary lesions. To investigate the hypothesis that local cellular immune response may affect presentation and outcome in tuberculosis, we performed bronchoalveolar lavage (BAL) in lung segments affected by cavitary and non-cavitary tuberculosis. We then correlated the type of cellular response at the level of the involved lung segments with clinical evolution in terms of cavity formation. We found alveolar lymphocytosis in patients with both cavitary and non-cavitary pulmonary tuberculosis, with increased CD4+ lymphocytes in patients with non-cavitary pulmonary tuberculosis. A predominant Th1 immune response has been observed in non-cavitary patients, while cavitary involved segments exhibit the presence of Th2 lymphocyte subsets. These data, while confirming the importance of Th1-type CD4+ cells and IFN-gamma in effective cellular immunity in active pulmonary tuberculosis, also suggest that the presence of Th2 lymphocytes may contribute to tissue necrosis phenomena associated with cavitary evolution of pulmonary tuberculosis. Our observations indicate the importance of the type of local immune response at the site of disease in the development of different clinical characteristics and outcome in pulmonary tuberculosis.

Adult↗
PubMed2003

Carcinoembryonic antigen mRNA analysis detects micrometastatic cells in blood from lung cancer patients.

The current authors previously identified circulating cells expressing carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) in 80% of lung cancer patients bearing distant metastases. The current study prospectively validated the data on a novel cohort and extended the study to other mRNAs expressed by neoplastic cells. CEA, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 (EPG2) mRNA was analysed by reverse transcriptase-polymerase chain reaction in circulating cells from 19 healthy controls, and in biopsies and blood at diagnosis from 32 lung cancer patients monitored for 24 months. Aldolase A and cytokeratin 19 mRNA occurred in circulating cells of all controls; cytokeratin 20 was not expressed by any lung cancer biopsy. EPG2 mRNA occurred in all biopsies but not in the patients' circulating cells. CEA mRNA occurred in 29/32 (90.6%) biopsies and in 17/32 mRNA samples from circulating cells from lung cancer patients. Of these positive patients 12/17 developed metastases within 9 months of mRNA analysis. Three positive patients died, one was lost to follow-up, and one did not develop metastases within 24 months. Of the negative patients 12/15 did not develop metastases during the 24-month follow-up; one patient was lost to follow-up, one did not express CEA, and another developed metastases. Unlike in other neoplasias, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 messenger ribonucleic acid are not useful for the detection of circulating cancer cells in lung cancer. Carcinoembryonic antigen messenger ribonucleic acid analysis in circulating cells helps to identify lung cancer patients at a greater risk of metastases.

Adenocarcinoma↗
PubMed2001

Human macrophage gamma interferon decreases gene expression but not replication of Mycobacterium tuberculosis: analysis of the host-pathogen reciprocal influence on transcription in a comparison of strains H37Rv and CMT97.

Mycobacterium tuberculosis is an intracellular pathogen that readily survives and replicates in human macrophages (MPhi). Host cells have developed different mycobactericidal mechanisms, including the production of inflammatory cytokines. The aim of this study was to compare the MPhi response, in terms of cytokine gene expression, to infection with the M. tuberculosis laboratory strain H37Rv and the clinical M. tuberculosis isolate CMT97. Both strains induce the production of interleukin-12 (IL-12) and IL-16 at comparable levels. However, the clinical isolate induces a significantly higher and more prolonged MPhi activation, as shown by reverse transcription-PCR analysis of IL-1beta, IL-6, IL-10, transforming growth factor beta, tumor necrosis factor alpha, and gamma interferon (IFN-gamma) transcripts. Interestingly, when IFN-gamma transcription is high, the number of M. tuberculosis genes expressed decreases and vice versa, whereas no mycobactericidal effect was observed in terms of bacterial growth. Expression of 11 genes was also studied in the two M. tuberculosis strains by infecting resting or activated MPhi and compared to bacterial intracellular survival. In both cases, a peculiar inverse correlation between expression of these genes and multiplication was observed. The number and type of genes expressed by the two strains differed significantly.

Gene Expression Regulation, Bacterial↗
PubMed2001

Tuberculosis and lung cancer. An interesting case study.

This report describes the case of a patient with lung cancer who completely recovered when he was suffering from tuberculosis. Since bacillus Calmette-Guerin (BCG) has beneficial effects in certain types of cancer, it was hypothesized that infection with Mycobacterium tuberculosis induced an effective response against the tumour. M. tuberculosis-infected blood T-lymphocytes of the patient were cultured with two lung tumour cell lines. T-lymphocytes in vitro remained attached to tumour cells that appeared reduced in number. Moreover, M. tuberculosis isolated from the patient was a strong inducer, in infected macrophages, of the expression of the inducible form of the nitric oxide synthase, that may regulate cytotoxic activity of human macrophages.

Aged↗
PubMed2001

Demographic risk factors and lymphocyte populations in patients with tuberculosis and their healthy contacts.

SETTING: Campania, a southern region of Italy, and the Institute of Respiratory Diseases, Monaldi Hospital, University 'Federico II', Naples. OBJECTIVE: To evaluate clinical and socio-demographic risk factors for tuberculosis (TB) infection and/or disease. Peripheral blood lymphocytes from a sub-cohort of 19 patients and 53 contacts were studied by flow cytometry. DESIGN: A prospective study among patients with newly diagnosed pulmonary tuberculosis and their close contacts. RESULTS: A total of 90 patients and 277 contacts were enrolled. The prevalence of infection was 45% (95%CI 39-51%) among contacts. Age, sex, delay in diagnosis and treatment, cavitation on chest radiograph, cough, unwillingness to cover the mouth, and volume of air shared by close contacts and patients were investigated as potential risk factors for infection. Only delay in diagnosis of cases remained independently associated with an increased risk of infection (P < 0.0002), and hemoptysis was the only factor capable of reducing the delay significantly. The CD8+ CD28+ cytotoxic subset was significantly diminished in the patients (P < 0.001), whereas the CD8+ CD28- and CD8+ CD57+ (suppressor and NK-like subsets) were elevated (P < 0.001 and P = 0.04). CONCLUSIONS: These data show that delay in diagnosis of cases is a crucial factor for tuberculosis and that cytotoxic CD8+ cells play a primary role in immune response to tuberculosis.

Adult↗
PubMed2000

P53 immunohistochemistry can identify bronchial dysplastic lesions proceeding to lung cancer: a prospective study.

Dysplasia is an important step in bronchial carcinogenesis and smokers present more dysplastic lesions than nonsmokers. These lesions not always lead to malignancy, so there is a need for additional, preferentially objective, diagnostic markers. To verify whether immunohistochemical overexpression of p53 protein in dysplastic areas could be a predictive marker of the development of lung cancer, we investigated p53 overexpression in 22 bronchial dysplastic lesions obtained by fibrebronchoscopy from heavy smokers who were not diagnosed as having lung cancer and were followed for a 4-yr period. Nine (41%) lesions showed p53-positivity. Seven lung cancers (78%), mostly squamous cell carcinomas, were detected within the follow-up in these patients and 3 in 13 (23%) patients with p53-negative lesions. Lung cancer occurred in all seven patients with dysplastic lesions showing >10% p53 positive nuclei. The positive predictive value of p53 immunostaining for lung cancer was 78%. The negative predictive value of p53 was 77%. p53 staining was not detected in squamous metaplasia lesions without atypia and in normal bronchial epithelium. Our findings provide evidence that p53-overexpression in bronchial dysplastic areas may be a clinically useful marker for identifying patients proceeding to, at least, squamous cell carcinoma and, in addition, may facilitate the detection of occult tumours.

Bronchi↗
PubMed2000

Mycobacterium tuberculosis and HIV co-infection in the lung: synergic immune dysregulation leading to disease progression.

There is evidence that Mycobacterium tuberculosis (Mtb) impacts on human immunodeficiency virus (HIV) infection and that HIV promotes mycobacterial diseases. Epidemiological and clinical studies demonstrate the detrimental effect of tuberculosis (TB) on the progression of HIV infection, that is an increased risk of death among Mtb-HIV co-infected patients. Pulmonary TB may occur very early during HIV infection, whereas extrapulmonary or atypical manifestations are associated with more profound immunodeficiency, showing features like mycobacteraemia and multi-drug resistance, much more severe than in immunocompetent hosts. During the last decade, many efforts have been focused on the immunological aspects of Mtb-HIV co-infection. The host protective response to TB is mediated by cell immunity, which, mainly supported by interleukin (IL)-12 and interferon (IFN)-gamma production, leads to granuloma formation. Perturbations in the cytokine expression, that is a reduced type-1-like response, have been suggested in HIV-infected patients to contribute to their susceptibility to TB. Indeed, an impaired balance between pro-inflammatory and anti-inflammatory cytokines and apoptosis-induced depletion of immune effector cells account for the dissemination of both the pathogens and for a poor granulomatous reaction in Mtb-HIV co-infected patients. However, the recently elucidated role of chemokines and their receptors in immune regulation opens new questions on the pathogenesis of Mtb-HIV co-infection.

Cytokines↗
PubMed1997

Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection.

Tuberculosis (TB) is still a major health problem, both as a single disease entity and as a cofactor in AIDS. The interaction between macrophage and Mycobacterium tuberculosis (MTB) is a critical step in the establishment of an early chronic infection. This study analyses the capacity of MTB to induce apoptosis in cells obtained by broncho-alveolar lavage (BAL) from patients with reactive pulmonary tuberculosis and from AIDS patients with disseminated pulmonary tuberculosis. Apoptosis was increased three-fold in BAL cells obtained from patients with pulmonary tuberculosis and even more markedly in alveolar macrophages of MTB-infected AIDS patients, compared with controls. Apoptosis was analysed and characterized by propidium iodide (PI) incorporation, terminal deoxy transferase (TDT)-mediated dUTP-biotin nick end labelling (TUNEL), and tissue transglutaminase (tTG) expression. The MTB-macrophage interaction was also investigated in vitro by infecting monocyte-derived macrophages (MDM) with MTB (virulent strain H37Rv). The induction of apoptosis by MTB required viable bacteria, was dose-dependent, and was restricted to H37Rv. Infection with either Mycobacterium avium complex (MAC) or HIV-1 and treatment with heat-killed MTB failed to induce apoptosis.

AIDS-Related Opportunistic Infections↗
PubMed1997

Lung cancer metastatic cells detected in blood by reverse transcriptase-polymerase chain reaction and dot-blot analysis.

PURPOSE: We analyzed the blood of patients with lung cancer at different stages of presentation for the presence of carcinoembryonic antigen (CEA) mRNA detected by reverse transcriptase-polymerase chain reaction (RT-PCR) combined with the dot-blot procedure as an indicator of micrometastatic malignant cells. PATIENTS AND METHODS: We studied 24 lung cancer patients (10 with distant metastases and 14 with no evidence of distant metastases), eight age- and sex-matched patients affected by nonneoplastic respiratory diseases (four smokers), and eight healthy subjects. We used immunohistochemistry and RT-PCR dot-blot analysis to evaluate CEA expression in the neoplastic tissue, and the RT-PCR dot-blot procedure to analyze CEA mRNA in circulating cells. RESULTS: The RT-PCR dot-blot procedure was highly sensitive aspecific: it detected CEA mRNA in samples of RNA from lung cancer diluted 10(6)-fold with RNA extracted from normal blood cells, and sequence analysis confirmed that the amplified product was CEA. CEA mRNA was found in circulating cells from eight of 10 lung cancer patients with distant metastases (diagnostic sensitivity, 80%) and in four of 14 patients with no evidence of distant metastases. Two of the latter had distant metastases within 6 months of analysis. Thus, the diagnostic specificity of the analysis toward lung cancer without distant metastases was 86%. The analysis was negative in the eight nonneoplastic patients and in the eight healthy controls. CONCLUSION: The RT-PCR dot-blot analysis of CEA mRNA in blood cells seems to be a promising tool for the early detection of micrometastatic circulating cells in patients with lung cancer.

Aged↗
PubMed1995

Epidemiology of lower respiratory tract infections.

The aim of this review is to focus on the epidemiology of lower respiratory tract infections, the etiology, prognosis and risk factors, dividing these problems into the following issues: global impact of these afflictions, community-acquired pneumonia, hospital acquired pneumonia, respiratory infections in surgery, acute bronchitis and exacerbations of chronic bronchitis. Every year about 5 million people die of acute respiratory infections. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Several factors (age, underlying disease, environment) influence mortality, morbidity and also microbial etiology. The authors also refer to recent data on the most frequently identified antibiotic resistance of respiratory pathogens. The knowledge of such different clinico-epidemiological situations is essential to physicians for an effective approach to treatment of pneumonia and bronchitis.

Adolescent↗
PubMed1991

Efficacy and safety of teicoplanin in gram-positive pulmonary infections.

Teicoplanin is a new antibiotic obtained from a culture filtrate of Actinoplanes teichomyceticus with potent activity against aerobic and anaerobic gram-positive bacteria and having a high affinity for healthy or inflamed bronchial mucosa and pulmonary parenchyma. To investigate the efficacy and safety of this drug, we selected 13 patients suffering from lower respiratory tract infections caused by gram-positive organisms. Pathogens isolated from sputum or bronchial aspirate were: 8 Staphylococcus aureus, 1 Staphylococcus epidermidis, 3 Streptococcus pneumoniae and 1 Streptococcus species. We began treatment as monotherapy at the dosage of 400 mg daily (200 mg x 2) I.M. only after microbiological evaluation. 11 patients (84.6%) were clinically and bacteriologically cured, 1 (7.7%) showed definite clinical improvement but persistence of causative agent and 1 (7.7%) failed to respond. The mean treatment period was 8.3 days. No major adverse effect was observed. We conclude that teicoplanin is a very efficacious and well-tolerated antibiotic for therapy of gram-positive pulmonary infections.

Adult↗
PubMed1989

Human basophil/mast cell releasability. V. Functional comparisons of cells obtained from peripheral blood, lung parenchyma, and bronchoalveolar lavage in asthmatics.

Releasability of human basophils and mast cells is an important parameter in allergic disorders. We compared IgE- and non-IgE-mediated releasability of human peripheral blood basophils with that of mast cells obtained from lung parenchyma (isolated by mechanical or enzymatic dissociation) and from bronchoalveolar lavage of normal and asthmatic donors. In a first study, the response to anti-IgE, Staph A, Con A, f-met peptide, and Ca2+ ionophore A23187 of basophils obtained from 52 donors was compared with that of mast cells isolated enzymatically (PMCE) or mechanically (PMCM) from lung parenchyma obtained during surgery. The histamine content of basophils (1.1 +/- 0.1 pg/cell) was significantly lower than that of PMCE (4.1 +/- 0.3 pg/cell; p less than 0.001) and PMCM (3.7 +/- 0.3; p less than 0.001). The maximal percent anti-IgE-induced histamine secretion in basophils (41.3 +/- 3.6) was higher than in PMCE (17.5 +/- 1.8) and in PMCM (13.8 +/- 1.5). Similarly, the response to Staph A and Con A was higher in basophils (29 +/- 3.9 and 31.6 +/- 4.9, respectively) than in PMCE (3.5 +/- 0.6 and 3.3 +/- 0.8, respectively) and PMCM (5.1 +/- 1.3 and 8.8 +/- 2.2, respectively). A positive correlation between the maximal percent of histamine release induced by anti-IgE and Staph A was found in basophils (rs = 0.61; p less than 0.001), whereas there was a negative correlation between the reactivity of PMCE (rs = 0.67; p less than 0.001) and PMCM (rs = -0.40; p less than 0.001) to anti-IgE and their reactivity to Staph A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Serodiagnosis survey of tuberculosis by a new ELISA method.

In a survey study, the authors used a new Elisa test, designed by Anda Biologicals, Strasbourg, France, to detect specific IgG and IgM antibodies against A60 antigen. Blood samples from 53 subjects were tested with this serological method: 22 with no tubercular diseases and 31 affected by different tubercular lesions. The IgM titers were negative in all control group subjects, in two out of fourteen patients with progressive primary tuberculosis, in thirteen out of sixteen with secondary tuberculosis and in one patient with extrapulmonary tuberculosis. The IgG titers were positive (greater than 1.25 Elisa units) in all cases, except one, of progressive primary tuberculosis, in all cases, except two, of secondary tuberculosis and in the patient affected by extrapulmonary tuberculosis. The performance of this method and the overall results indicate its sensitivity and reliability to detect specific mycobacterial antibodies at different stages of the disease.

Adolescent↗
PubMed1987

A comparative study of ofloxacin versus cefazolin in lower respiratory tract infections.

An open study was conducted in 40 randomized patients to evaluate the efficacy of ofloxacin in comparison with cefazolin in the treatment of acute, chronic and recurrent lower respiratory tract infections. The therapeutic efficacy of the two drugs was evaluated on the basis of bacteriological and clinical examinations. Bacteriological assays revealed that ofloxacin eliminated bacterial flora from sputum in 20/21 cases (14 Gram-negative and 7 Gram-positive), while cefazolin eradicated the pathogens in 12/19 cases (16 Gram-negative and 3 Gram-positive). In clinical terms, 20/21 (95.2%) infections were cured and 1/21 (4.8%) improved in the ofloxacin group as against 12/19 (63.2%) cured, 5/19 (26.3%) improved and 2/19 (10.5%) unchanged in the cefazolin group. The results of this study confirm the efficacy and excellent tolerance of ofloxacin in the treatment of lower respiratory tract infections.

Adult↗
PubMed1986

Evaluation of the efficacy of the combination of fenoterol and ipratropium bromide (Duovent) in asthmatic subjects.

The efficacy of the combination of fenoterol and ipratropium bromide (Duovent) versus placebo was evaluated in 20 asthmatic subjects. A double-blind crossover design was used during 2-day experimental evaluation: on the 1st day all patients were given a double metered dose of each preparation (Duovent and placebo) by an inhaler, with a 30-min interval; on the 2nd day the sequence of administration was reversed. The functional parameters were evaluated before administrations and at 30, 60 and 90 min after the first administration. The investigation showed that Duovent had a noticeable bronchodilating activity at 30 min, further increasing at 60 and 90 min, without the occurrence of side-effects.

Adult↗
PubMedDate not supplied

Exhaled breath condensate as matrix for toluene detection: a preliminary study.

The study was designed to investigate whether exhaled breath condensate, obtained by cooling exhaled air in spontaneous breathing, could be a suitable matrix for toluene quantitative analyses. Nine healthy subjects were exposed for a short period (20 min) to a known concentration of toluene. Exhaled breath condensate samples were collected before and at the end of the exposure, while the environmental concentration of toluene was continuously monitored. Toluene was analysed by head-space gas-chromatography mass spectrometry, and assay repeatability was also estimated in vitro. Baseline and post-exposure measurement of hippuric acid, the urinary toluene metabolite, was performed to assess current toluene exposure. Before the exposure toluene concentrations in the exhaled breath condensate were lower than the detectable limit in all subjects, while after the exposure toluene was detectable with a median value 0.35 microg l-1 (range 0.15-0.55 microg l-1) in all the exhaled breath condensate samples. As compared with the standard calibration in distilled water, the curves obtained by exhaled breath condensate were linear and comparable with the range examined in vivo for toluene. A significant correlation was found between the environmental toluene levels and toluene in the exhaled breath condensate at the end of exposure. Furthermore, a significant relationship between increased exhaled breath condensate toluene levels and urinary hippuric acid after the exposure was found. In conclusion, exhaled breath condensate is a promising matrix for toluene assessment, although its application in humans requires further investigations.

Adult↗