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Biomedical subjects

G Mazzarella

Publications and source records attributed to G Mazzarella.

At least 37 records · Page 2Linked to original sources

Subpleural lung involvement in Behçet's disease: first localization of a systemic entity.

Behçet's disease (BD) is a chronic multisystem vasculitis, affecting many organs and the vascular system, of unknown aetiology. Eyes, skin, joints, the oral cavity, the central nervous system, and, less frequently, heart, lung, kidney, the genital system and the gastrointestinal tract can be involved. Intrathoracic manifestations of BD consist mainly of thromboembolism of the superior vena cava and/or other mediastinal veins; aneurysms of the aorta and pulmonary arteries; pulmonary infarct and haemorrhage; pleural effusion; and, rarely, myocardial and/or hilar lymphoid involvement. In the present case, the patient presented with BD with an asymptomatic subpleural lung mass and bilateral pulmonary artery enlargement. The patient was treated with a combination of surgical and medical therapy with complete resolution of the lung involvement and without any parenchymal relapses after an 8-month follow-up.

Behcet Syndrome↗

Quercetin and anti-CD95(Fas/Apo1) enhance apoptosis in HPB-ALL cell line.

Several malignant cell lines are resistant to CD95-(Apo1/Fas)-mediated apoptosis, even when the CD95 receptor is highly expressed. Sensitivity to CD95-induced apoptosis can be restored using different molecules. In this study, we showed that quercetin, a naturally occurring flavonoid, in association with the agonistic anti-CD95 monoclonal antibody, increases DNA fragmentation and caspase-3 activity in HPB-ALL cells. These cells have been selected for their known resistance to CD95-induced apoptosis. At molecular level, quercetin lowers the level of intracellular reactive oxygen species, reduces mitochondrial transmembrane potential, thereby leaving the expression of CD95 receptor unchanged.

Apoptosis↗

Influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in COPD.

We examined the influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 microg puff(-1)), or placebo. Two hours after inhalation, a dose-response curve to inhaled oxitropium bromide (100 microg puff(-1)) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 microg oxitropium bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 microg + oxitropium bromide 600 microg, (2) formoterol 12 microg + placebo, (3) formoterol 24 microg + oxitropium bromide 600 microg, (4) formoterol 24 microg + placebo, (5) placebo + oxitropium bromide 600 microg, or (6) placebo + placebo. Both formoterol 12 microg and 24 microg induced a good bronchodilation (formoterol 12 microg, 0.19-0.20 l; formoterol 24 microg 0.22-0.24 l). The dose-response curve of oxitropium, but not placebo, showed an evident increase in FEV1, with a further significant increase of respectively 0.087 l and 0.082 l after the formoterol 12 microg and formoterol 24 microg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding oxitropium 400-600 microg to formoterol. There is not much difference in bronchodilation between combining oxitropium with formoterol 12 microg or 24 microg. In any case, formoterol 24 microg alone seems sufficient to achieve the same bronchodilation induced by oxitropium 600 microg alone in most patients.

Administration, Inhalation↗

Majority of gliadin-specific T-cell clones from celiac small intestinal mucosa produce interferon-gamma and interleukin-4.

An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8-, TCR alphabeta+. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-gamma; the remaining one initially produced only IL-4, but subsequently also IFN-gamma. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-gamma, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.

Adolescent↗

Gliadin activates mucosal cell mediated immunity in cultured rectal mucosa from coeliac patients and a subset of their siblings.

BACKGROUND: CD3 and gamma delta cells in the rectal mucosa increase after local instillation of gluten in children with coeliac disease and in half of their siblings. Aim- To establish an in vitro system for assessing immunological changes induced by gluten in the rectum. PATIENTS AND METHODS: Rectal biopsy specimens obtained from 13 treated coeliac children, nine of their siblings, and nine controls were cultured in vitro with a peptic-tryptic digest of gliadin or ovalbumin. CD3 and CD25 cells were counted, and the expression of adhesion molecules evaluated. RESULTS: In the lamina propria of coeliac biopsy samples cultured with gliadin, but not in those from controls, the expression of vascular cell adhesion molecule 1 (VCAM-1) was enhanced, and the number of CD25 cells was significantly higher than in those cultured in medium alone; the density of intraepithelial CD3 cells was also significantly higher. No differences were noted in coeliac biopsy specimens cultured with ovalbumin. A discriminant analysis allowed correct classification of all controls and all coeliacs but one, but three of nine siblings were allocated to the coeliac group. CONCLUSIONS: Our data confirm that gliadin is able to activate cell mediated immunity in the rectal mucosa in coeliac patients and in a subset of their first degree relatives.

Adolescent↗

Viruses and asthmatic syndromes.

Viruses are recognized to be the major cause of respiratory infections. Clinical and experimental evidence also supports an important role for viruses in the pathogenesis of lower airway disease and asthma exacerbation. In prospective epidemiological studies, 80% of asthma exacerbations in school-aged children and half of all asthma exacerbations in adults have been associated with viral upper respiratory infections. Human rhinovirus (HRV) has been implicated as the principal virus associated with asthma exacerbation. In our studies on respiratory viruses, we have observed two clinical patterns of presentation. The viruses can either be a precipitating factor of respiratory illness characterized by a typical clinical onset, or can induce an atypical clinical onset such as haemoptysis, pleuritis, spontaneous pneumothorax and asthmatic syndrome. Thus the observed clinicoradiological and functional features during atypical viral respiratory infection may be correlated to the long-term biological effects induced by previous and concurrent infections.

Acute Disease↗

Role of monocyte/macrophage population in immune response.

The central role of macrophages in host defence against infection and malignancy and processes such as atherosclerosis, makes macrophage biology a fascinating area for research in immunology and cell biology. The endocytic and phagocytic machinery of macrophages is particularly potent and their secretory potential is large and diverse. Studies of cell surface receptors and their role in antigen presentation, microbicidal and tumouricidal activity are actively researched and progress is now being made in defining receptors responsible for monocyte/macrophage cell adhesion within the immune system. This short-review highlights the recent advances in macrophage biology.

Endocytosis↗

Prognostic value of p53 in non-small cell lung cancer: relationship with proliferating cell nuclear antigen and cigarette smoking.

p53 mutations are among the most frequent genetic alterations reported in human lung cancer. Although the prognostic value of altered p53 expression is still debated, it is accepted widely that estimation of the proliferation rate has an important prognostic role. Moreover, an association between certain types of human lung cancers and tobacco use is well known. Drawing from this background, we investigated the immunohistochemical expression of mutant oncogenic p53 protein, and related it to the smoking history of 61 patients with non-small cell lung carcinoma (NSCLC) and to the expression pattern of proliferating cell nuclear antigen (PCNA), which is considered to be an important negative prognostic factor in several neoplasms. We found p53 overexpression in 22 (36.1%) specimens, including 16 squamous carcinomas (41%) and six (27.2%) adenocarcinomas. PCNA nuclear staining was detected in 98.4% of the specimens, and a significantly higher PCNA expression score was found in all of the p53-positive samples. When the patient survival time was compared, p53 accumulation had a statistically significant negative prognostic value (P < .001). This was supported by a Kaplan-Meier survival percentage plot of immunohistochemically p53-undetectable specimens and p53-detectable specimens. These latter patients had a greatly reduced survival time. A relationship was established between p53 immunohistochemical detection and the smoking history of the patients. None of the specimens from the nonsmoking patients expressed immunohistochemically detectable p53 protein. Altered p53 expression was detected in 40.7% of smoking patients. Our findings support the hypothesis of involvement of p53 mutations in tobacco-induced carcinogensis and indicate that altered p53 expression plays an important prognostic role in NSCLC in smokers.

Biomarkers, Tumor↗

Identical T-cell receptor beta chain rearrangements are present in T cells infiltrating the jejunal mucosa of untreated celiac patients.

The intestinal mucosal lesion in celiac disease is characterized by a predominant T-cell infiltration of both epithelium and lamina propria. However, a restricted use of T-cell receptors (TCR) in T lymphocytes infiltrating the jejunal mucosa of celiac patients has not been reported. Based on an immunohistochemical survey of jejunal biopsies from a cohort of untreated celiac patients, we demonstrated a small but significant increase of V beta 8.1/2+ T cells in the lamina propria, but not in the epithelium nor in the peripheral blood. Sequence analysis indicated the existence of a variable degree of clonality of V beta 8+ T cells in the celiac mucosa. More importantly, the recurrence of identical CDR3 regions in some patients was also observed. The altered distribution of V beta 8+ T cells and the presence of identical CDR3 regions in celiac patients, but not in controls was independently confirmed by CDR3 size analysis in a further cohort of patients. These findings suggest that disease-specific variations of the TCRBV8 repertoire are present in the small intestinal mucosa of untreated celiac patients.

Amino Acid Sequence↗

Modulation of cytokine production in activated human monocytes by somatostatin.

The immunosuppressor effects of the widely distributed neuropeptide somatostatin were examined on purified peripheral blood human monocytes. Somatostatin, at concentrations thought to be physiologic (10(-10)-10(-7) M), regulated monocyte/macrophage responses to (LPS) stimulation, as reflected by interleukin production. In particular, somatostatin had direct inhibitory effects on TNF-alpha, IL-1 beta, and IL-6 secretion by LPS-activated monocytes, while the decrease on IL-8 synthesis was modulated mainly by the action of somatostatin on TNF-alpha and IL-1 beta. In fact, the addition of these two inflammatory cytokines to the monocyte culture medium was able to induce IL-8 expression, as demonstrated by mRNA analysis, also in presence of the neuropeptide. Although somatostatin affected IL-8 production in an indirect way, it suppressed directly the chemotactic response of neutrophils to IL-8. Finally, somatostatin downregulation of monocyte activation was confirmed by the decrease of HLA-DR expression on cell plasma membranes (52% versus 33%). Our results confirm that somatostatin exerts preferential effects on the suppression of immunoreactions by modulating cytokine production and activity.

Cells, Cultured↗

In siblings of celiac children, rectal gluten challenge reveals gluten sensitization not restricted to celiac HLA.

BACKGROUND & AIMS: Inflammatory changes in the rectum of patients with celiac disease after local instillation of gluten have been reported. The aim of this study was to examine rectal mucosa after local gluten challenge in children with celiac disease and their siblings. METHODS: Rectal biopsy specimens were obtained before and 6 hours after rectal challenge with a peptictryptic digest of gliadin in 33 children with treated celiac disease, 12 controls, and 19 siblings of children with celiac disease. Epithelium and lamina propria volumes were determined, and CD3+ and gamma delta + lymphocytes were counted. RESULTS: After local instillation of gliadin, a significant increment in the absolute number of intraepithelial lymphocytes was noted in patients with celiac disease but not in controls. Immunohistochemical analysis showed a significant increase in CD3+ and gamma delta + cells, with the gamma delta/CD3 ratio remaining unchanged after challenge. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis was used to classify 6 of 13 siblings as having celiac disease. The positivity was not associated with the presence of the heterodimer encoded by the DQA*0501 DQB1*0201 alleles in any of the siblings. CONCLUSIONS: All patients with celiac disease were identified by rectal gluten challenge. Approximately half of the siblings reacted to rectal instillation of gluten. The genetic background of such sensitization to gluten remains to be elucidated.

Adolescent↗

Differential expression of the retinoblastoma gene family members pRb/p105, p107, and pRb2/p130 in lung cancer.

The Rb (retinoblastoma) gene family is composed of three members: the RB gene (one of the best-studied tumor suppressor genes) and two related genes, p107 and pRb2/p130. These three proteins share many structural and functional features and play a fundamental role in growth control. Using immunocytochemical techniques, we evaluated a variety of lung tumor specimens for the expression of this family of proteins and compared protein expression with the histological grading of the tumors and with the expression of the proliferating cell nuclear antigen. These Rb family members displayed distinctive patterns when compared and contrasted using different parameters. The highest percentage of undetectable levels in all of the specimens examined and the tightest inverse correlation (P) with the histological grading and with proliferating cell nuclear antigen expression in the most aggressive tumor types were found for pRb2/p130, which may suggest an important role for this protein in the pathogenesis and progression of lung cancer.

Animals↗

Breast feeding and acute lower respiratory infection.

The association between breast feeding and acute lower respiratory infection (ALRI) was studied in a case-control study in southern Italy. Two groups of children were studied: the first group comprised 73 infants, aged 0-6 months, whose diagnosis was pneumonia or bronchiolitis; the second group included 88 infants less than 12 months of age with a diagnosis of pertussis-like illness. Control infants were two groups of infants admitted to the same ward. Compared with controls, infants in the first group were less likely to have been breast fed (odds ratio 0.42, 95% CI 0.19-0.90). The protection conferred by breast feeding was stronger among infants who were receiving human milk at the time of admission (odds ratio 0.22, 95% CI 0.09-0.55) and was absent among those infants who had stopped breast feeding for two or more weeks before admission. Among infants who were severely ill, breast feeding was less likely than among those with milder illnesses. There was evidence in the stratified analysis of effect modification by the presence of other children in the family. Among the infants with pertussis-like illness, the incidence and duration of breast feeding were not different compared with controls. The results suggest that breast feeding has a strong protective effect against ALRI in industrialized countries also. No protection seems to be conferred by human milk against pertussis-like illness.

Acute Disease↗

Protective effects of nedocromil sodium on cellular and biohumoral components present in the bronchial alveolar lavage fluid and in peripheral blood in atopic asthmatics.

Nedocromil sodium, a disodium salt of a pyroquinolinedicarboxylic acid, raises the bronchial hyperresponsiveness threshold, because it inhibits the mediators released by the various cells, and reduces the involvement and activation of inflammatory cells. The aim of this study was to evaluate the state of activation of the immunocompetent cells and the main chemical mediators present in the bronchoalveolar lavage (BAL) fluid from 10 atopic asthmatic patients, before and after treatment with nedocromil sodium. The following examinations were performed before treatment and after 120 days of therapy with nedocromil sodium at 16 mg/day (two 2-mg puffs x 4): the level of chemical mediators and the state of activation of immunocompetent cells in BAL fluid; immunological analytes in activation of immunocompetent cells in BAL fluid; immunological analytes in peripheral blood; aspecific bronchial challenge test with ultrasonicated bidistilled H2O fog to evaluate variations in the hyperreactivity threshold; questionnaire to determine any adverse effects of treatment (cough, breathlessness, sleep disorders). Our findings demonstrate that nedocromil sodium prevents the release of chemotactic and inflammatory mediators by the effector cells and thus stabilizes microvascular permeability and epithelial damage, so raising the threshold of response to bronchoconstriction stimuli. Lastly, nedocromil sodium is associated with a better preventive therapeutic efficacy and good tolerance and can therefore be suggested as a valid drug to be used in the long-term treatment of bronchial asthma.

6-Ketoprostaglandin F1 alpha↗

Infant feeding and idiopathic intussusception.

A case-control study showed that, compared with infants who had never been fed human milk, breast-fed infants had a relative risk of intussusception of 6.0 (95% confidence interval, 1.8 to 20.4) when breast-feeding at admission was exclusive and of 2.3 (95% confidence interval, 0.8 to 6.6) when it was partial. Exclusive breast-feeding may be a risk factor for intussusception in infancy.

Bottle Feeding↗

Phenotypic features and secretory pattern of alveolar macrophages in atopic asthmatic patients.

The aim of this study was to evaluate by cytofluorimetry, the phenotype and the activation of alveolar macrophages (CD14; CD33; CD44; CD54; CD23; HLA-DR) and, by radioimmunoassay, the "in vivo and in vitro" macrophage secretory pattern (IL-1 alpha; IL-1 beta; IL6; IL8; PGE2; PGD-1 alpha; TXB2; LTB4) in atopic patients with mild asthma in intercritical phase and with bronchial hyperreactivity (PD20 FEV1 = 377 +/- 262.8 micrograms). In asthmatic patients we have demonstrated that the number of cells recovered in BALF expressing the phenotypic features (CD14; CD33; HLA-DR; CD23; CD44; CD54) was larger than in control subjects. By analysing the culture medium of unstimulated and LPS-stimulated alveolar macrophages from asthmatic and normals we have demonstrated a greater production of IL-1 beta (p = 0.005) and IL-8 (p = 0.005) in the first group than in one second, as confirmed by a Wilcoxon test. Concerning the secretory pattern in BALF of asthmatic patients we obtained similar results, showing a significant IL-1 beta (p = 0.005) and IL-8 (p = 0.002) increase suggesting a persistent cellular activation. On the contrary we could not show any significant increase of IL-1 alpha (p = 0.31) and IL-6 (p = 0.22). The cellular activation was confirmed by increased levels of different chemical mediators such as TXB2 (p = 0.005); LTB4 (p = 0.004); PGE2 (p = 0.007); PGF-1 alpha (p = 0.008) which were recovered from BALF of asthmatic patients compared to normal subjects. In conclusion alveolar macrophages play an important role in the pathogenesis of asthma because of the presence of cytokines and mediators in BALF and in the supernatant of alveolar macrophage cultures.

Adult↗

Breast-feeding and urinary tract infection.

A case-control study was conducted to study the association between breast-feeding and urinary tract infection. Case patients were 128 infants aged birth to 6 months with urinary tract infection. Control infants were 128 infants admitted to the same ward with an acute illness. The results support the hypothesis that breast-feeding protects infants against urinary tract infection.

Bottle Feeding↗