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Biomedical subjects

A Bruno

Publications and source records attributed to A Bruno.

At least 19 recordsLinked to original sources
PubMed2006

Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas.

Ras oncogenes are frequently mutated in thyroid carcinomas. To verify the role played by N-ras in thyroid carcinogenesis, we generated transgenic mice in which a human N-ras(Gln61Lys) oncogene (Tg-N-ras) was expressed in the thyroid follicular cells. Tg-N-ras mice developed thyroid follicular neoplasms; 11% developed follicular adenomas and approximately 40% developed invasive follicular carcinomas, in some cases with a mixed papillary/follicular morphology. About 25% of the Tg-N-ras carcinomas displayed large, poorly differentiated areas, featuring vascular invasion and forming lung, bone or liver distant metastases. N-ras(Gln61Lys) expression in cultured PC Cl 3 thyrocytes induced thyroid-stimulating hormone-independent proliferation and genomic instability with micronuclei formation and centrosome amplification. These findings support the notion that mutated ras oncogenes could be able to drive the formation of thyroid tumors that can progress to poorly differentiated, metastatic carcinomas.

Adenocarcinoma, Follicular↗
PubMed2006

Somatosensory- and motor-evoked potential monitoring during spine and spinal cord surgery.

STUDY DESIGN: Prospective, observational study. SETTING: Regional Trauma Center, Torino, Italy. OBJECTIVES: Complex spinal surgery carries a significant risk of neurological damage. The aim of this study is to determine the reliability and applicability of multimodality motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) monitoring during spine and spinal cord surgery in our institute. METHODS: Recordings of MEPs to multipulse transcranial electrical stimulation (TES) and cortical SEPs were made on 52 patients during spine and spinal cord surgery under propofol/fentanyl anaesthesia, without neuromuscular blockade. RESULTS: Combined MEPs and SEPs monitoring was successful in 38/52 patients (73.1%), whereas only MEPs from at least one of the target muscles were obtained in 12 patients (23.1%); both MEPs and SEPs were absent in two (3.8%). Significant intraoperative-evoked potential changes occurred in one or both modalities in five (10%) patients. Transitory changes were noted in two patients, whereas three had persistent changes, associated with new deficits or a worsening of the pre-existing neurological disabilities. When no postoperative changes in MEP or MEP/SEP modalities occurred, it was predictive of the absence of new motor deficits in all cases. CONCLUSION: Intraoperative combined SEP and MEP monitoring is a safe, reliable and sensitive method to detect and reduce intraoperative injury to the spinal cord. Therefore, the authors suggest that a combination of SEP/MEP techniques could be used routinely during complex spine and/or spinal cord surgery.

Adolescent↗
PubMed2006

Anger and ego-defence mechanisms in non-psychiatric patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is commonly accepted as a disorder closely influenced by affective factors, which can either trigger the symptoms or contribute to their persistence, independently from their aetiology. It has been previously documented that irritable bowel syndrome patients respond to a variety of emotional states (anger, fear and anxiety) with an increase in colonic motility. AIMS: The aim of this study was to evaluate the experience and the expression of anger and the prevalent ego-defence mechanisms in a group of non-psychiatric patients with irritable bowel syndrome. SUBJECTS: Fifty-two patients with irritable bowel syndrome (18 males, 34 females) and 100 healthy volunteers from the community (44 males, 56 females) matched for age, level of education and social-status were enrolled. METHODS: Assessment was conducted using the State-Trait Anger Expression Inventory and the Defence Mechanism Inventory. RESULTS: No important differences between the two examined groups were found using the State-Trait Anger Expression Inventory and Defence Mechanism Inventory. CONCLUSIONS: It can be hypothesised that stable personality features and habits, such as anger disposition and defence mechanisms, play only a marginal role in irritable bowel syndrome, while psychological and psychosocial influences may act as predisposing or precipitating factors which contribute to the pathogenesis or expression of irritable bowel symptoms.

Adult↗
PubMed2006

Evaluation of biological features of cord blood units collected with different methods after cesarean section.

INTRODUCTION: Cord blood banks are established worldwide as a result of the increased use of umbilical cord blood (UCB) transplantation. The outcomes of this procedure relate to the cell dose of the UCB unit and the UCB collection. The aim of this study was to evaluate whether the mode of collection influenced the biological features of the UCB units. MATERIALS AND METHODS: We studied 151 UCB units consecutively collected in the cesarean setting with two different methods: in utero after infant delivery and before delivery of the placenta, and ex utero after delivery of placenta. RESULTS: Sixty-nine UCB units were collected in utero and 82 ex utero. The two groups were comparable for maternal and obstetric factors. The proportion of banked UCB units was similar in the two groups (38% vs 40%, respectively). No statistically significant differences were observed between the methods of collection in term of volume, white blood cell count, total nucleated cell content, CD34(+) cells, and CFU-GM. CONCLUSION: This preliminary study showed that the two methods of collection in the cesarean setting were overlapping and valid if performed according to standard operating procedures.

Cesarean Section↗
PubMed2006

Hypoallergenic fragment of Par j 2 increases functional expression of Toll-like receptors in atopic children.

BACKGROUND: Parietaria judaica (Par j) is one of the main causes of allergy in the Mediterranean countries. The activation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) inhibits nasal inflammation of atopic children. OBJECTIVE: To examine, in vivo and in vitro, the effect of recombinant Par j 2 (rPar j 2) and of its fragments (1-55 and 52-102) on atopic children. METHODS: We used skin prick test for in vivo evaluations. We assessed, in vitro, in peripheral blood mononuclear cells (PBMC), the effect of rPar j 2 and of the two fragments on neutrophil chemotaxis, on CD45RO, on TLR2 and TLR4 expression, on LPS binding and on interferon (IFN)-gamma release, by a microchemotaxis chamber, by flow cytometry and by enzyme-linked immunosorbent assay, respectively. RESULTS: In vivo while rPar j 2 induced a positive skin reaction, 1-55 and 52-102 fragments did not. In vitro, while rPar j 2 increased both CD45RO expression and neutrophils chemotaxis in PBMC, both Par j 2 fragments did not. 1-55 fragment of Par j 2 upregulated both TLR2 and TLR4 expression and LPS binding, while the rPar j 2 and 52-102 fragment did not. Finally, 1-55 fragment of Par j 2 induced IFNgamma release, while the rPar j 2 and 52-102 fragment did not. CONCLUSIONS: Hypoallergenic 1-55 fragment, upregulating innate immunity receptors and increasing IFNgamma, might re-orientate, in atopics, the immune system toward a physiologic balance between Th1 and Th2 responses.

Adolescent↗
PubMed2006

Effect of MCM09, an active site-directed inhibitor of factor Xa, on B16-BL6 melanoma lung colonies in mice.

BACKGROUND: Treatment with anticoagulant drugs has shown potential inhibitory effect on tumor invasion, although the relationship with clotting inhibition was not clear. AIM: The aim of our study was to evaluate the potential antitumor activity of MCM09, a newly developed, active site-directed, small molecule inhibitor of factor Xa (FXa) [WO0216312], and to relate the findings to anticlotting potency. METHODS: MCM09 (0.1-10 mg kg(-1)) or heparin (H; 10 mg kg(-1)) was injected intravenously (i.v.), with 5 x 10(4) B16-BL6 melanoma cells, in C57BL/6 mice. Mice were killed after 18 days, to count lung colonies. Ex vivo anticoagulant activity was measured by activated partial thromboplastin time (APTT) on mouse plasma. RESULTS AND CONCLUSIONS: MCM09, a selective inhibitor of FXa (IC-50 = 2.4 nm against human FXa), inhibited in a dose-dependent manner B16-BL6 melanoma lung colonies in mice. Mean lung metastasis number was 20.9 +/- 4.8 in controls (n = 10), 1.2 +/- 0.4 in mice treated with H, 10 mg kg(-1) i.v. (P < 0.01), 0.9 +/- 0.3, 9.2 +/- 2.2 and 15.5 +/- 2.6 in mice treated with MCM09, at 10 (P < 0.01), 1 (P < 0.05) and 0.1 mg kg(-1) i.v. (ns), respectively. MCM09 (10 mg kg(-1) i.v.) significantly prolonged APTT (57.1 +/- 10.2 s) 30 min after i.v. injection when compared with controls (25.3 +/- 1.6 s; P < 0.05). Lung colonies were 74.2-72.6% reduced by MCM09 (10 mg kg(-1)) given 60 or 120 min before cells, but not by MCM09 given 60 min thereafter, suggesting a direct cell interaction as a mechanism underlying antitumor activity.

Animals↗
PubMed2006

Association between burnout and anger in oncology versus ophthalmology health care professionals.

The prevalence of burnout in oncology staff was compared with that of the ophthalmology staff, who normally present a low prevalence of burnout as described in this literature. The correlation of burnout with the emotion of anger was also investigated. Thirty-six subjects working in an oncology department and 32 working in an ophthalmology department were examined using the Maslach Burnout Inventory and the State-Trait Anger Expression Inventory. The oncology group showed higher mean scores on the MBI Emotive Exhaustion and Depersonalization scales with respect to ophthalmology staff. Correlation analysis showed that increasing burnout was associated with higher anger expressed towards the environment and loss of anger control. Anger, as a response to frustration, appears to be a feature constantly associated with the clinical expression of burnout and it should not be underestimated in theoretical and preventive contexts.

Adult↗
PubMed2006

Defense mechanisms in hemodialysis-dependent patients.

Defense mechanisms are automatic psychological processes that protect the individual against anxiety and from the awareness of internal or external dangers or stressors. The influence of defense mechanisms in patients on chronic hemodialysis treatment was studied. There were 53 uremic subjects (37 males and 16 females), aged between 22 and 88 years (mean age 60.11, SD 15.03), on chronic dialysis and 50 healthy subjects as controls have been enrolled in the study. According to the duration of dialysis, uremic patients were divided in two subgroups: 21 patients with less than 5 years and 19 patients with more than 10 years of dialytic treatment. Assessment was conducted using the Defense Mechanisms Inventory DMI. The inventory identifies five defensive styles: turning against the object (TAO), projection (PRO), principalization (PRN), turning against the self (TAS) and reversal (REV). Results showed DMI scores within the normal range both for uremics and controls with significant differences in TAO (t = -3.053, p = 0.003) and REV (t = 5.067, p < 0.0001) between groups. No significant differences in the use of defensive styles related to the duration of dialytic treatment were observed. Besides other psychological features, the assessment of defense mechanisms in patients with chronic and invalidating diseases may contribute to ameliorate the knowledge of the adjustment processes and of the psychological well-being of the patients.

Adult↗
PubMed2005

Carotid endarterectomy--an evidence-based review [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the efficacy of carotid endarterectomy for stroke prevention in asymptomatic and symptomatic patients with internal carotid artery stenosis. Additional clinical scenarios, such as use of endarterectomy combined with cardiac surgery, are also reviewed. METHODS: The authors selected nine important clinical questions. A systematic search was performed for articles from 1990 (the year of the last statement) until 2001. Additional articles from 2002 through 2004 were included using prespecified criteria. Two reviewers also screened for other relevant articles from 2002 to 2004. Case reports, review articles, technical studies, and single surgeon case series were excluded. RESULTS: For several questions, high quality randomized clinical trials had been completed. Carotid endarterectomy reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis (16% absolute risk reduction at 5 years). There is a smaller benefit for patients with 50 to 69% symptomatic stenosis (absolute risk reduction 4.6% at 5 years). There is a small benefit for asymptomatic patients with 60 to 99% stenosis if the perioperative complication rate is low. Aspirin in a dose of 81 to 325 mg per day is preferred vs higher doses (650 to 1,300 mg per day) in patients undergoing endarterectomy. CONCLUSIONS: Evidence supports carotid endarterectomy for severe (70 to 99%) symptomatic stenosis (Level A). Endarterectomy is moderately useful for symptomatic patients with 50 to 69% stenosis (Level B) and not indicated for symptomatic patients with <50% stenosis (Level A). For asymptomatic patients with 60 to 99% stenosis, the benefit/risk ratio is smaller compared to symptomatic patients and individual decisions must be made. Endarterectomy can reduce the future stroke rate if the perioperative stroke/death rate is kept low (<3%) (Level A). Low dose aspirin (81 to 325 mg) is preferred for patients before and after carotid endarterectomy to reduce the rate of stroke, myocardial infarction, and death (Level A).

Aspirin↗
PubMed2005

Lack of association of CCR gene polymorphisms and left ventricular hypertrophy in essential hypertension.

Left ventricular hypertrophy (LVH) is a major determinant of heart damage. Scientific evidence suggests the influence of genetic factors, but these have yet to be completely clarified. This study investigates a possible relationship between LVH and two chemokine receptor (CCR) gene polymorphisms: CCR5delta32 and CCR264I. Essential hypertensive out-patients (n=118, grade I-II, age 27-54) were recruited from the Catholic University Hypertension Centre. For each subject, clinical data on office blood pressure and M-mode/2D echocardiography were collected. Statistical analysis did not show a significant association between the CCR polymorphisms and LVH in the study population.

Adult↗
PubMed2005

Does leptin play a cytokine-like role within the airways of COPD patients?

The leptin-leptin receptor system might be up-regulated in the airways of chronic obstructive pulmonary disease (COPD). In bronchial biopsies obtained from normal subjects and smokers, with and without COPD, the present study examined leptin and leptin-receptor expression and their co-localisation in airway and inflammatory cells. Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end-labelling techniques, apoptosis in airway and inflammatory cells and in leptin and leptin-receptor expressing cells was investigated. In the epithelial cells both leptin and leptin-receptor expression was higher in normal subjects than in smokers and COPD subjects. By contrast, in the sub-mucosa, leptin was over-expressed in COPD when compared with normal subjects and smokers. Leptin and its receptor were co-localised, mainly with activated T cells (CD45R0) and CD8+ T lymphocytes. In smokers, apoptosis was found in some inflammatory cells, whereas in COPD inflammatory cells, leptin and leptin-receptor positive cells were not apoptotic. Leptin expression was related to COPD severity and assessed using the Global initiative for Chronic Obstructive Lung Disease classification. In conclusion, the present study shows an increased leptin expression in bronchial mucosa of chronic obstructive pulmonary disease patients, associated with airway inflammation and airflow obstruction.

Adult↗
PubMed2004

Nerve growth factor-induced protein kinase C stimulation contributes to TrkA-dependent inhibition of p75 neurotrophin receptor sphingolipid signaling.

Previous studies have established that reciprocal interactions between the low-affinity p75 nerve growth factor (NGF) receptor (p75(NTR)) and the high-affinity TrkA NGF receptor can dictate the cellular response to NGF. As the most important interaction, TrkA signaling was found to inhibit p75(NTR)-mediated sphingomyelinase (SMase) stimulation, ceramide production, and apoptosis. However, the mechanism by which TrkA counteracts p75(NTR)-coupled sphingolipid signaling is still unclear. Considering the stimulatory effect of NGF on protein kinase C (PKC) activity, we investigated the role of PKC in TrkA/p75(NTR) signaling interaction. In this study, we found that, in SK-N-BE cells, which selectively express p75(NTR), phorbol ester-induced PKC stimulation resulted in the abrogation of SMase stimulation and ceramide production induced by NGF. Moreover, in SK-N-BE neuroblastoma cells, which selectively express TrkA, NGF stimulated global PKC activity through two independent pathways involving phospholipase Cgamma (PLCgamma) and phosphoinositide-3 kinase (PI3K). In SH-SY5Y, another neuroblastoma cell line, which coexpresses TrkA and p75(NTR), NGF induced PKC stimulation through a TrkA/PI3K signaling pathway, whereas there was no ceramide production. However, in these cells, the inhibition of TrkA, PI3K, and PKC resulted in the restoration of NGF-induced ceramide production. Thus, our study demonstrates for the first time that TrkA interferes with p75(NTR) signaling through a PI3K/PKC-dependent mechanism.

Cell Line, Tumor↗
PubMed2004

Panic-agoraphobic spectrum in obese binge eaters.

OBJECTIVE: This study investigated the frequency of the panic-agoraphobic spectrum symptoms in a sample of obese subjects affected by Binge Eating Disorder (BED) vs controls. METHOD: Fifty obese with BED were matched by age, sex and marital status to twenty-five normal weight controls. The Structured Clinical Interview For Panic-Agoraphobic Spectrum--SCI-PAS was administered to all participants. RESULTS: Obese subjects with BED presented significantly higher frequencies of typical and atypical panic symptoms (82% vs 8%, p<0.0001), agoraphobia (58% vs 12%, p=0.002) and reassurance orientation (56% vs 8%, p=0.001) than controls. DISCUSSION: BED frequently co-occurs with other major psychiatric disorders, traditionally assessed using categorical methods of classification of mental disorders. The spectrum of the subthreshold, atypical and partial symptoms of full-blown mental disorders, often neglected by categorical approach, may also affect subjective well-being and functioning as full-blown disorders. The identification of the subthreshold symptomatology may have relevant implications for the response to treatment and the outcome of the eating disorder.

Adult↗
PubMed2004

Description of a flow cytometry approach based on SYBR-14 staining for the assessment of DNA content, cell cycle analysis, and sorting of living normal and neoplastic cells.

RATIONALE: This study aimed to expand the utilization of a simplified flow cytometric approach that employing SYBR-14/PI staining into broader flow cytometry applications, including (i) measurement of the DNA content; (ii) performing cell cycle analysis on mammalian cells; and (iii) sorting of live SYBR-14-stained mammalian cells based on DNA content. MATERIAL AND METHODS: Cell lines of human origin were stained with SYBR-14 and propidium iodide (PI) and assessed by a dual-color flow cytometry. Finally, sorting of living SYBR-14-stained human cell lines was performed. RESULTS: Dual staining with SYBR-14 and PI of human cells followed by flow cytometry analysis demonstrates that in addition to quality assessment, this staining could be utilized to determinate the DNA content on mammal cells. In addition, it resolves the diploid, tetraploid, and aneuploid DNA content. Furthermore, the SYBR-14-stained mammal cells were efficiently sorted based on DNA content and live cells were obtained. All these features have not been previously described with the utilization of this staining approach. CONCLUSIONS: Results of this study demonstrate that this flow cytometric approach not only allows assessment of the viability of cells, but also the DNA content of mammal cells. In addition, this approach allows one to sort viable cells stained with SYBR-14. These findings open-up unexpected and unrestricted avenues for sorting of living mammal cells and provide significant advantages over the traditionally cumbersome sorting approaches for living cells, which demand very specialized and expensive UV light sources as well as sophisticated sorting procedures.

Cell Cycle↗
PubMed2004

Functional and structural characterization of two populations of human monocyte-derived dendritic cells.

BACKGROUND: The characterization of human monocyte-derived dendritic cells (HM-DC) subsets have been a very difficult and elusive task because of the lack of appropriate reagents. We, therefore utilized several diverse approaches to evaluate two populations of HM-DC including flow cytometry, ultra-structural evaluation by electron microscopy, and functional assays. In addition, we studied the kinetics of the expression of antigens on HM-DC at diverse intervals of time and identify surface markers and functional differences of these two HM-DC subsets. RESULTS: This study identified that a phenotype of HM-DC as defined by CD11c+, CD86+, and CD40+ could be separated in the presence or absence of TGF-beta1 into two different subsets of DC: (i) HM-DC without Birbeck granuli (Mo-DC) and (ii) HM-DC with Birbeck granuli (Mo-LC). Furthermore, the functional studies showed that the HM-DC treated with TGF-beta1 (Mo-LC) exhibited the presence of Birbeck granuli and could actively divide. In addition, after undergoing more than four cell divisions, these cells split into at least two additional subsets of Mo-LC: (iia) Mo-LC with high forward scatter (FSC) and (iib) Mo-LC with normal FSC. In contrast, the Mo-DC cultured in absence of TGF-beta1 did not exhibit Birbeck granuli, showed reduced ability to divide, and kept the normal FSC when analyzed. CONCLUSIONS: This study enabled us to determine in HM-DC: (i) the existence of antigenic and functional differences between various subpopulations of Mo-DC and Mo-LC; (ii) the existence of differences in the kinetics of antigens expression among the subsets of Mo-DC and Mo-LC; (iii) the existence of specific markers for each of the subpopulations of HM-DC.

Antineoplastic Agents↗
PubMed2004

In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics.

BACKGROUND: Corticosteroids play an important role in inflammation and remodelling of airways and are considered an important therapeutic target in asthma. Inflammation in asthma is characterized by a dysregulation of eosinophil apoptosis and of markers of airways remodelling. We evaluated the ability of flunisolide to inhibit in vitro the release of metalloproteinases-9 (MMP-9), tissue inhibitor metalloproteinases-1 (TIMP-1), transforming growth factor (TGF-beta) and fibronectin by sputum cells (SC) as well as to induce sputum eosinophil apoptosis. METHODS: The SC, isolated from induced sputum samples of 12 mild-to-moderate asthmatics, were cultured for 24 h in the presence or absence of flunisolide (1, 10 and 100 microM). The release of mediators was assessed by enzyme-linked immunosorbent assay (ELISA) whereas apoptosis was studied by TUNEL technique. RESULTS: Flunisolide (10 microM) significantly reduced MMP-9 and TIMP-1 (P = 0.0011 and P < 0.0001 respectively) and increased MMP-9/TIMP-1 molar ratio (P = 0.004). In addition, flunisolide decreased TGF-beta and fibronectin release by SC (P = 0.006; and P < 0.0001 respectively) and increased eosinophil apoptosis (P < 0.001). CONCLUSIONS: These results demonstrate that flunisolide may play an important role in the inhibition of airway inflammation and remodelling, by promoting the resolution of eosinophilic inflammation and by inhibiting the release of MMP-9, TIMP-1, TGF-beta and fibronectin.

Adult↗
PubMed2004

Inflammatory features of nasal mucosa in smokers with and without COPD.

BACKGROUND: To investigate whether nasal and bronchial inflammation coexists in chronic obstructive pulmonary disease (COPD), nasal and bronchial biopsy specimens from seven control subjects, seven smokers without COPD, and 14 smokers with COPD were studied. METHODS: Nasal and bronchial biopsy specimens were taken from the same patients during bronchoscopy and squamous cell metaplasia and the thickness of the epithelium and basement membrane were measured. The numbers of eosinophils (EG2), neutrophils (elastase), macrophages (CD68), and CD8 T lymphocytes (CD8/144B) were assessed by immunohistochemistry. RESULTS: Smokers with and without COPD had squamous metaplasia in the nasal and bronchial epithelium. In all groups the thickness of the nasal epithelium was greater than that of the bronchial epithelium. The thickness of the basement membrane was similar in nasal and bronchial biopsy specimens from smokers with and without COPD, but was greater in the bronchi than in the nasal epithelium of controls. Eosinophil number was higher in the nasal and bronchial mucosa of smokers without COPD than in smokers with COPD or controls. Neutrophil number was higher in the nasal and bronchial mucosa of smokers with COPD than in smokers without COPD or controls. CD8 T lymphocyte numbers were similar in smokers with and without COPD and higher than in controls. There were fewer macrophages in nasal and bronchial biopsy specimens from smokers without COPD than in those with COPD. CONCLUSION: Nasal and bronchial inflammation coexists in smokers and is characterised by infiltration of CD8 T lymphocytes. In smokers without COPD this feature is associated with an increased number of eosinophils, while in those with COPD it is linked to an increased number of neutrophils in both nasal and bronchial biopsy specimens.

Adult↗