PubMed Health⌕ Search

Biomedical subjects

A Baldi

Publications and source records attributed to A Baldi.

At least 37 records · Page 2Linked to original sources
PubMed2004

Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers.

AIMS: Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis-related factors. In this study we evaluated the possible role of p53 and Bcl-2 gene family members as prognostic factors for non-small-cell lung cancer. METHODS AND RESULTS: We investigated the immunohistochemical expression of p53 and Bcl-2 gene family members (bax, Bcl-2 and Bcl-xL) in 94 non-small-cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl-2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over-expression of bax and Bcl-xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl-2, bax or Bcl-xL or with patient survival time. CONCLUSIONS: This study confirms a relevant role for apoptosis-regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl-2 as a prognostic factor for this tumour.

Apoptosis↗
PubMed2004

Effect of vitamin E supplementation on various functional properties of macrophages and neutrophils obtained from weaned piglets.

Sixteen piglets were used to determine the effect of vitamin E supplementation on several functional properties of macrophages and neutrophils obtained from weaned piglets. Piglets, immediately following weaning, were assigned to one of three experimental groups: control (no vitamin E supplementation), low level of vitamin E supplementation (100 mg DL-alpha-tocopheryl acetate/kg diet) and high level of vitamin E supplementation (300 mg DL-alpha-tocopheryl acetate/kg diet). Supplementation of vitamin E lasted for a period of 36 days, following a 3-day adaptation period after weaning. Blood samples were collected on days 0, 12, 24 and 36 of the experimental period, monocytes/macrophages and neutrophils were isolated and the following parameters were determined in macrophages and neutrophils activated by phorbol myristate acetate: total cell-associated and membrane-bound urokinase plasminogen activator (u-PA) activity and superoxide anion production. Results showed that macrophages and neutrophils isolated from piglets that received supplemental vitamin E had higher (P < 0.05) total and membrane-bound u-PA activities as well as higher (P < 0.05) superoxide anion production compared with the values of the corresponding cells obtained from control piglets on day 12 of the experimental period. Both levels of vitamin E supplementation (low and high) were equally effective. In contrast, vitamin E supplementation had no effect (P > 0.05) on total and membrane-bound u-PA activities and superoxide anion production by porcine macrophages and neutrophils on days 24 and 36 of the experimental period. In conclusion, the low level of vitamin E supplementation is recommended for piglets for the first 2 weeks after weaning.

Animals↗
PubMed2004

Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks.

The aim of the study was to verify the production of PAF and the activity of PAF acetyl-hydrolase (PAF-AH), the enzyme involved in the catabolism of this phospholipid mediator, in migraine attacks. Their levels were determined during migraine crises in serial samples of internal jugular venous blood taken from five migraine patients without aura, who were admitted to the hospital during the crises. Internal jugular venous blood samples were taken immediately after catheter insertion at 1, 2, and 4 h after attack onset, and within 2 h from its cessation. PAF was purified by high-performance liquid chromatography (HPLC) and determined by radioimmunoassay method. The enzymatic activity of PAF-AH was measured by reverse-phase HPLC, based on the derivatization with 7-diethylaminocoumarin-3-carbonylazide. In the internal jugular venous blood of migraine patients without aura (MO), an increase was observed in PAF levels, which was already evident at the time of catheter insertion (885.6 +/- 82.8) and at the first hour (868.4 +/- 65.24) (ANOVA: P < 0.0001). PAF levels remained elevated through the second (746.8 +/- 82.95), fourth (700.6 +/- 34.93) and sixth hours (644.4 +/- 42.85), and then decreased at the end of the attack, reaching levels significantly lower than those measured at the time of catheter insertion (565.5 +/- 38.34). The activity of PAF-AH showed an opposite trend with higher values at the first hour and significantly lower values at the second and fourth hours from the beginning of the migraine attack (ANOVA: P < 0.02). The increased production of PAF may account for persistent platelet activation during migraine crises, even in the presence of an increased production of nitric oxide (NO) end-products which, on the other hand, should instead intervene in counteracting and limiting platelet activation. Potential sources of PAF production are the endothelial cells from cerebral vessels, stimulated by trigeminal neuropeptides, platelets themselves, and mast cells, as suggested by the neurogenic inflammation model.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2004

Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?

BACKGROUND: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia. OBJECTIVE: To assess COX-2 expression at the site of recent myocardial infarction. METHODS: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10-60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3. RESULTS: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0-25.4%) v 3.7% (0.6-12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-alpha staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035). CONCLUSIONS: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause-effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.

Aged↗
PubMed2004

Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer.

AIMS: To evaluate the prognostic impact of tumour angiogenesis assessed by vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumour vessel invasion in patients who had undergone radical resection for stage IB-IIA non-small cell lung cancer (NSCLC). METHODS: Fifty one patients (42 men, nine women; mean age, 62.3 years; SD, 6.9) undergoing complete surgical resection (35 lobectomy, 16 pneumonectomy) of pathological stage IB (n = 43) and IIA (n = 8) NSCLC were evaluated retrospectively. No patient underwent postoperative chemotherapy or neoadjuvant treatment. Tumour specimens were stained for VEGF and specific MVD markers: CD31, CD34, and CD105. RESULTS: VEGF expression significantly correlated with high CD105 expression (p < 0.0001) and tumour vessel invasion (p = 0.04). Univariate analysis showed that those patients with VEGF overexpression (p = 0.0029), high MVD by CD34 (p = 0.0081), high MVD by CD105 (p = 0.0261), and tumour vessel invasion (p = 0.0245) have a shorter overall survival. Furthermore, multivariate Cox regression analysis showed that MVD by CD34 (p = 0.007), tumour vessel invasion (p = 0.024), and VEGF expression (p = 0.042) were significant predictive factors for overall survival. Finally, the presence of both risk factors, tumour vessel invasion and MVD by CD34, was highly predictive of poor outcome (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.5; p = 0.0002). CONCLUSIONS: High MVD by CD34 and tumour vessel invasion are more closely related to poor survival than the other neoangiogenetic factors in stage IB-IIA NSCLC. This may be because these factors are more closely related to the metastatic process.

Adult↗
PubMed2004

Mediastinal hibernoma: a case report.

Hibernomas are rare benign tumours that arise most often in adults from the remnants of fetal brown adipose tissue. They usually affect muscle and subcutaneous tissue and are asymptomatic and slow growing. The distribution of this tumour follows the sites of persistence of brown fat. Out of more then 100 cases described in the word literature only three hybernomas were mediastinal. A recent clinicopathological study of 170 cases from the Armed Forces Institute of Pathology confirmed the exceptionality of the intrathoracic location. This report describes a very rare case of mediastinal hibernoma in a young man.

Adult↗
PubMed2004

Surviving acute myocardial infarction: survivin expression in viable cardiomyocytes after infarction.

BACKGROUND: Apoptosis is a key feature in postinfarction remodelling leading to progressive myocyte loss. Both proapoptotic and antiapoptotic factors contribute to the delicate balance between death and survival. The survivin pathway has emerged as essential in the control of apoptosis, although its role in heart disease is unknown. AIM: To evaluate survivin expression after acute myocardial infarction (AMI). METHODS: Survivin expression was assessed immunohistochemically in the peri-infarct and remote viable myocardium in 17 consecutive patients who died 1-30 weeks after AMI and in four control hearts. RESULTS: Survivin was expressed by myocytes in the peri-infarct area in eight patients and in the remote region in 13 patients. The rate of survivin expression after AMI was significantly higher in the remote versus peri-infarct regions and compared with control hearts. Its expression was inversely associated with the presence of dilated cardiopathy and of apoptosis, independently from the gross pathology infarct size. CONCLUSIONS: Survivin myocardial expression after AMI may be associated with the survival of at risk myocardium and may be indicative of more favourable remodelling after AMI. These findings identify a potential new target for the treatment of postinfarction remodelling.

Apoptosis↗
PubMed2004

Analysis of cell cycle regulator proteins in non-small cell lung cancer.

BACKGROUND/AIMS: Abnormalities of the proteins involved in cell cycle checkpoints are extremely common among almost all neoplasms. This study aimed to investigate the expression of four components of the cell cycle machinery-p21, p16, p53, and proliferating cell nuclear antigen (PCNA)-in non-small cell lung cancer (NSCLC). METHODS: The expression of p21, p16, p53, and PCNA was examined in 68 well characterised NSCLC specimens using immunohistochemistry. The coregulation of these proteins and their influence on survival were analysed using both univariate and multivariate analyses. RESULTS: By univariate analysis, the expression of all the proteins examined, except for PCNA, was significantly correlated with survival. In multivariate analysis, the only immunohistochemical parameter able to influence overall survival was p16, confirming the hypothesis that the RB-p16 tumour suppressor pathway is inactivated in most lung cancer samples. Finally, the group of patients with NSCLC who were negative for both p21 and p16 had a significantly shorter overall survival. CONCLUSIONS: These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancers, and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumour suppression.

Adult↗
PubMed2004

Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma.

BACKGROUND: A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of cyclooxygenase-2 (COX-2) and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53. METHODS: Immunohistochemistry was used to determine the expression of COX-2 and p27. The correlation with survival of these factors and of p21 and p53 expression was assessed by univariate and multivariate analyses. RESULTS: A positive statistically significant correlation was found between p27 and p21 expression (p<0.0001), but there was a negative correlation between COX-2 expression and both p27 (p = 0.001) and p21 (p<0.0001). No statistically significant correlation was recorded between p53 and all the other immunohistochemical parameters. Univariate analysis showed that overall survival was strongly influenced by p21, p27, and COX-2 expression, but multivariate Cox regression analysis showed that the only immunohistochemical parameter to influence overall survival of patients with mesothelioma was COX-2. CONCLUSIONS: These findings suggest that COX-2 expression may be a useful prognostic parameter for mesothelioma.

Cell Cycle Proteins↗
PubMed2003

High-risk clinical features predict increased post-infarction myocardial apoptosis and the benefits as a result of an open infarct-related artery.

BACKGROUND: Infarct-related artery (IRA) patency after acute myocardial infarction (AMI) is associated with a more favourable clinical course, in particular in patients with high-risk features. As it has been recently reported that IRA patency is associated with a reduced postinfarction apoptotic rate (AR), the aim of our study was to assess whether IRA status late after AMI had a different impact on AR in high- vs. low-risk patients. METHODS AND RESULTS: Co-localization of TUNEL and caspase-3 was used to calculate the AR at the site of infarction at the time of death in 30 subjects. The Norris coronary prognostic index (NI) was calculated (computing age, presence of pulmonary congestion, heart size and history of previous additional AMI) in order to define the patients' individual risk at the time of hospitalization. According to the NI (< or =7 vs. >7), subjects were divided into low and high risk, as NI >7 carries an approximate threefold higher risk of death. The NI was significantly correlated with the AR at the time of death both in infarct and remote areas. Twenty subjects had IRA occlusion at the time of death, and in these patients AR was significantly higher both in infarct and remote areas (P<0.001 and P=0.009 vs. the others, respectively). However the impact of IRA occlusion on AR was significantly different comparing high- vs. low-risk subjects. In particular, AR at the infarct site was 10-fold higher in the high-risk subjects with IRA occlusion (26.1%[20.4-28.7%]) vs. those with open IRA (2.3%[0.6-3.5%]; P=0.002) and was nonsignificantly different in the low-risk subjects vs. those without IRA occlusion (8.2%[2.5-17.5%] vs. 5.4%[1.5-7.9%]; P=0.48). Similarly, in the high-risk subjects, AR in remote areas was significantly greater in cases with occluded vs. open IRA (0.7%[0.4-0.9%] vs. 0.3%[0.3-0.32%]; P=0.009). CONCLUSION: A significantly higher AR is associated with IRA occlusion late post AMI in subjects with high-risk clinical features, and not in low-risk patients. The diverse impact of IRA occlusion on AR in subjects with different risk profiles may explain the greater benefit associated with coronary reperfusion in high-risk subjects. The overall lower AR in low-risk subjects, independently from the IRA status, may be correlated with the better long-term prognosis after AMI in this case.

Aged↗
PubMed2003

Rumen-protected choline administration to transition cows: effects on milk production and vitamin E status.

We investigated the influence of rumen-protected choline (RPC) supplementation on milk production, lipid metabolism and vitamin E status in dairy cows receiving a silage-based diet. Twenty-six Italian Holstein multiparous cows were assigned by weight and average production in the previous lactation, to one of two groups: control (no RPC supplementation) and RPC (supplemented with 20 g/day rumen-protected choline chloride). Treatment began 14 days before expected calving and continued for 30 days after parturition. Choline administration significantly increased milk production during the first month of lactation and also the concentration (and total secretion) of choline in milk, but did not affect fat or protein concentrations in milk, or plasma levels of glucose, beta-hydroxybutyrate, cholesterol and non-esterified fatty acids (NEFA). However, around parturition, NEFA concentrations in plasma were lower in treated animals than in controls, suggesting improved lipid metabolism as a result of choline supplementation. Choline supplementation also increased alpha-tocopherol plasma concentrations, suggesting a novel aspect in dairy cows.

Animal Nutritional Physiological Phenomena↗
PubMed2003

The eukaryotic initiation factor 5A is involved in the regulation of proliferation and apoptosis induced by interferon-alpha and EGF in human cancer cells.

Interferon-alpha (IFNalpha) can induce apoptosis, a process regulated by a complex network of cell factors. Among these, eukaryotic initiation factor-5A (eIF-5A) is peculiar because its activity is modulated by the post-translational formation of the amino acid hypusine. Here we report the effects of IFNalpha and epidermal growth factor (EGF) on apoptosis and eIF-5A activity in human epidermoid oropharyngeal KB and lung H1355 cancer cells. We found that 48-h exposure to 1000 and 2000 IU/ml IFNalpha induced about 50% growth inhibition and apoptosis in H1355 and KB cells, respectively, and the addition of EGF completely antagonized this effect. When IFNalpha induced apoptosis, a hyperactivation of MEK-1 and ERK signalling and a decrease of the hypusine-containing form and, thus, of eIF-5A activity were recorded. The latter effect was again antagonized by the addition of EGF to IFNalpha-pretreated cells, probably through the activation of the EGF-->ERK-dependent pathway, since the addition of the specific MEK-1 inhibitor PD098059 abrogated the recovery of intracellular hypusine content induced by EGF in IFNalpha-pretreated cancer cells. Subsequently, we evaluated if the hypusine synthesis inhibitor (and eIF-5A inactivator) N1-guanyl-1,7-diaminoheptane (GC7) synergized with IFNalpha in the induction of cell growth inhibition and apoptosis. The analysis of the isobologram of IFNalpha and GC7 demonstrated a strong synergism between the two drugs in inducing cell growth inhibition. We also found that GC7 and IFNalpha had a synergistic effect on apoptosis. These data suggest that the apoptosis induced by IFNalpha could be regulated by eIF-5A that, therefore, could represent a useful target for the potentiation of IFNalpha antitumor activity.

Antineoplastic Agents↗
PubMed2003

Right ventricular dilatation after left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at postmortem examination in humans.

BACKGROUND: Cardiac remodelling after acute myocardial infarction (AMI) is characterised by molecular and cellular mechanisms involving both left and right ventricles, and biventricular failure identifies patients with an extremely unfavourable prognosis. AIMS: To assess whether a link exists between increased myocardial apoptotic rates (AR) at sites of recent infarction and patterns of unfavourable cardiac remodelling, such as biventricular enlargement after left ventricular (LV) infarction. METHODS: Twelve patients with recent AMI involving the LV and not the right ventricle (RV) and with permanent infarct related artery occlusion were selected at necropsy. Gross pathological characteristics, such as LV and RV dilatation, and AR at site of infarction were assessed. Potential false positive results (DNA synthesis and RNA splicing) were excluded from the cell count. RESULTS: RV enlargement, defined as a tricuspidal ring greater than 120 mm, was found in five cases and was associated with LV dilatation. These patients showed significantly higher AR than the others. When the subjects were divided into three groups according to progressive cardiac remodelling (absence of cardiac dilatation, isolated LV dilatation, and biventricular enlargement), the last group had significantly higher ARs than the other two groups, showing that myocardiocyte apoptosis is increased in more unfavourable forms of cardiac remodelling. CONCLUSION: Patients with severely unfavourable cardiac remodelling, such as biventricular enlargement, have extremely high myocardiocyte apoptosis at necropsy, even late after LV myocardial infarction, supporting the role of myocardiocyte loss in determining post-infarction adverse remodelling.

Aged↗
PubMed2003

Prevention of radiotherapy-induced emesis.

In this minireview the authors examine and discuss the radioprotective compounds and the new combination therapies for the prophylaxis of radiation-induced emesis. Radiation-induced emesis is an important secondary effect of this anticancer treatment and it represents one of the causes of therapy interruption and decay of life quality before the introduction of optimal control of radiation-induced emesis with new antiemetic drugs which ensure the continuance of radiotherapy and avoid time breaks, that could negatively influence the efficacy of anticancer treatment. The incidence, the severity or the latency of radiotherapy-induced nausea and vomiting are correlated both with the treatment features (fractions, total dose, irradiation site) and with the main clinical characteristics of the patients. In contrast to the very extensive literature on the prevention of chemotherapy-induced emesis, relatively few studies about the prevention of nausea and vomiting in patients submitted to radiotherapy have been published. Among antiemetic drugs for the prevention of emesis, benzamides and in particular metoclopramide, are widely used in clinical practice. The introduction of selective 5-HT3 antagonists in clinical practice produced an important improvement in control of chemotherapy induced emesis, but few published studies were aimed at evaluating the efficacy of these drugs in the prophylaxis of nausea and vomiting due to radiation exposure. We herewith present a brief summary of Clinical practice guidelines for the use of antiemetics in anticancer therapy recently published by ASCO (American Society of Clinical Oncology).

Antiemetics↗
PubMed2003

Pleomorphic adenoma of cervical heterotopic salivary glands.

Neoplastic transformation of heterotopic cervical salivary gland tissue is extremely rare. The Authors describe a case of pleomorphic adenoma arising in this tissue, on the right side of the neck in a 40-year old man. The characteristics of salivary heterotipias of the neck, and their diagnostic difficulties and histogenetic problems are reviewed.

Adenoma, Pleomorphic↗