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Biomedical subjects

A Camerini

Publications and source records attributed to A Camerini.

12 recordsLinked to original sources
PubMed2006

Analysis of dystroglycan regulation and functions in mouse mammary epithelial cells and implications for mammary tumorigenesis.

Abnormalities in the interactions of cells with the extracellular matrix (ECM) play an important role in the development and progression of many types of cancer and are a hallmark of malignant transformation. The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the ECM to the actin cytoskeleton, providing structural integrity and perhaps transducing signal, in a manner similar to integrins. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor differentiation and aggressiveness. In breast cancer, reduced DG expression has been associated with patient survival and with loss of differentiation of tumor cells. Limited data are available on DG physiology in epithelial cells. In this study, we used the HC11 spontaneously immortalized murine mammary epithelial cells to study DG function(s) and regulation in normal cells. We found that expression of DG protein and mRNA is cell-cycle and cell-density regulated in these cells. Moreover, expression of both DG subunits increased upon lactogenic differentiation of the HC11 cells. The turnover of cell-surface-expressed DG was evaluated in the same cells and half-life of DG subunits was evaluated to be about 12 h. DG-specific small inhibitory RNAs were used to analyze the effects of a reduced expression of DG in these cells. Cells in which DG expression was suppressed were growth inhibited, accumulated in the S-phase of the cell cycle, failed to undergo lactogenic differentiation, and displayed an increase in the percentage of apoptotic cells. Moreover, changes were observed in the expression and/or activity of several molecules involved in cell growth control. These results demonstrate that DG expression is tightly regulated in normal mammary epithelial cells and support the hypothesis that DG is involved in several functions other than structural integrity in these cells. This finding provides new insight into the roles played by DG in epithelial cell physiology and will contribute to our understanding of its involvement in the process of epithelial cell transformation.

Animals↗
PubMed2003

Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts.

Cell cycle progression in eukaryotic cells is regulated by a family of cyclin-dependent kinases (CDKs). Cyclin E is a regulatory subunit of CDK2 and drives cells from G1 to S phase. Increased expression of cyclin E is a frequent event in human malignancies and has been associated with poor prognosis in various cancers. In this study, we evaluated the effects of cyclin E-overexpression on the sensitivity of rat fibroblasts to anticancer drugs. Cyclin E-overexpressing cells were less sensitive to doxorubicin-induced inhibition of cell growth but not to other antineoplastic drugs, such as paclitaxel, vincristine, etoposide and methotrexate. Cyclin E-overexpressing fibroblasts also displayed a reduction in ROS levels and a significantly lower increase following doxorubicin treatment compared with vector control cells. The expression of manganese superoxide dismutase (MnSOD) and its activity were increased (about 1.3-fold) in cyclin E-overexpressing derivatives compared with control cells. These results suggest that cyclin E overexpression might reduce tumour cells sensitivity to doxorubicin by affecting the expression of MnSOD and that determination of cyclin E expression levels might help to select patients to be treated with an anthracycline-based antineoplastic therapy.

Animals↗
PubMed2001

[Use of digitalis in chronic heart failure: an unresolved problem?].

The role of digitalis in the treatment of patients with heart failure is still being debated. The DIG study, a trial which enrolled about 6800 patients with the aim at overcoming the doubts on efficiency and safety of digoxin, showed a neutral effect on mortality but there was a statistically significant decreased risk of hospitalization due to worsening heart failure in the digoxin group compared to the placebo group. The trial disclosed several problems about patient selection (many patients were on digitalis before the start of the trial), digoxin dosage, which seemed to be high, and about the true reported beneficial effects of this therapy. Finally the data available do not permit any evaluation on the use of beta-blockers and the association between digitalis and beta-blockers considering the properties of these drugs in suppressing orthosympathetic activation.

Cardiotonic Agents↗
PubMed1998

Panoramic coronary angiography.

OBJECTIVES: We describe a new imaging technique for coronary angiography. BACKGROUND: The conventional approach to coronary angiography exploits static perspective imaging over multiple cardiac cycles, using a limited number of empirically selected views. This approach entails both lack and redundancy of information and may result in suboptimal visualization of the individual lesion, contributing to diagnostic inaccuracy. METHODS: We developed a new imaging technique exploiting dynamic perspective, obtained by transverse 180 degree rotation of the C arm of a conventional angiographic unit during standard selective coronary opacification and filming. This technique yields a picture of the coronary tree isocentrically rotating around the longitudinal axis and conveying complete three-dimensional information. RESULTS: A complete diagnostic run for both coronary arteries, including two 25 degree cranial and two 25 degree caudal scans is accomplished with a total cine time of 16 s and 45 ml of contrast medium, about half of that required by conventional angiography. In a series of 129 consecutive patients studied by both the conventional and the new technique with quantitative measurements of the severity of the stenoses, the final diagnosis was identical in 65. In no case was a stenosis detected only by the conventional approach. However, in 31 patients the new technique permitted identification of 34 critical stenoses (79+/-8% [mean +/- SD]) either underestimated (61+/-3% n = 24, p < 0.001) or undetected (21+/-22%, n = 10, p < 0.001) in the standard projections. In a further 28 cases, 33 subcritical lesions (60+/-5%) were visualized in the rotational images but were insignificant (24+/-22% p < 0.001) in the standard projections. In five additional patients, distinct laminar plaques were clearly visualized only by the panoramic approach. CONCLUSIONS: This new technique can be easily implemented on conventional angiographic equipment at no additional cost. It provides complete, operator-independent exploitation of the angiographic information, resulting in enhanced diagnostic accuracy.

Coronary Angiography↗
PubMed1994

[The prognostic stratification of the risk of sudden death and sustained ventricular tachycardia after an acute myocardial infarct: which patients should undergo programmed ventricular stimulation?].

BACKGROUND: Programmed ventricular stimulation performed early after acute myocardial infarction allows to identify patients at risk of sudden death and sustained ventricular tachycardia with high degree of predictive accuracy. This procedure, however, because of its invasive nature, is not desirable as a screening test for large numbers of patients. Therefore, it should be performed on a smaller group of postinfarction patients preselected on the basis of noninvasive testing. The aim of the present study was to identify, early after acute myocardial infarction, any procedure among noninvasive testing, able to selected with the highest sensitivity patients at risk of sudden death and sustained ventricular tachycardia to submit to programmed ventricular stimulation. METHODS: Two hundred and sixty four consecutive patients with recent myocardial infarction were evaluated and followed during a period of 12 months. In each patient 48 epidemiological, clinical and laboratory variables were evaluated. Laboratory variables were acquired between the 7th and the 12th day after the acute event. RESULTS: Multiple linear regression analysis showed that only Killip class, the number of ventricular premature depolarizations per hour and the presence of ventricular late potentials were significantly and independently related to the occurrence of sudden death and sustained ventricular tachycardia (F = 18.7; p < 0.00001). Combinations of these variables, determined at cut off levels best discriminating two subgroups of patients at different risk of the end-point events, proved to be able to accurately predict the outcome of our patients. The presence of at least one of the following conditions: Killip class > or = 2, ventricular premature depolarizations > or = 30 per hour, ventricular late potentials allowed to identify a first subgroup of patients at risk with a sensitivity of 100% (p = 0.00007), whereas the presence, at the same time, of all the above mentioned parameters allowed to identify a second subgroup of patients at risk with a 44% of positive predictive value (p = 0.00007). CONCLUSIONS: Our findings suggest that the first subgroup of postinfarction patients selected on the basis of noninvasive testing should undergo programmed ventricular stimulation, the second might be treated by adequate antiarrhythmic therapy without undergo any further investigation, whereas the remaining patients (without late potentials, in Killip class 1 and with ventricular premature depolarizations < 30 per hour) might be discharged without any antiarrhythmic therapy.

Aged↗
PubMed1992

Predicting cardiac mortality after uncomplicated myocardial infarction by exercise radionuclide ventriculography and exercise-induced ST segment elevation.

In 183 consecutive patients with recent, uncomplicated myocardial infarction, the following variables were associated with 4-year cardiac death: haemodynamic decompensation with exercise (P = 0.01), left ventricular ejection fraction at rest (P = 0.004) and at peak exercise (P = 0.003), persistent ST segment elevation at rest in the area of infarction = (P = 0.004), exercise-induced ST segment elevation (P = 0.02), and late aneurysmal evolution (P = 0.01). Exercise left ventricular ejection fraction was the sole variable selected by Cox regression analysis as an independent predictor of cardiac death. In 40 patients with ST segment elevation at rest, left ventricular ejection fraction was 42 +/- 17% at rest and 40 +/- 18% at peak exercise, versus 52 +/- 12% and 52 +/- 14% in the remaining patients (both P less than 0.01). Among these 40, 16 (all with anterior infarction) also had exercise-induced ST segment elevation; their ejection fraction was 32 +/- 13% at rest, 30 +/- 13% during exercise, versus 53 +/- 15% and 53 +/- 15% in 129 patients with no ST segment elevation either at rest, or during exercise (both P less than 0.01). The 4-year risk of death was 20% in the former 40 patients, 36% in the latter 16, while in the complete absence of ST segment elevation, such risk was 3%. All 14 patients with ST segment elevation only during exercise were alive after 4 years: their left ventricular ejection fraction was 47 +/- 12% at rest, 45 +/- 13% with exercise. ST segment elevation was associated with late aneurysmal evolution but not with exercise-induced ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea↗
PubMed1989

[On the possibility of accelerating thrombolytic therapy in the acute phase of myocardial infarction: efficacy of and tolerance to the infusion of 1.5 million units of streptokinase in 30 minutes].

To evaluate efficacy and tolerability of the systemic infusion of 1,500,000 streptokinase units in 30', we treated 26 consecutive patients with acute myocardial infarction within 3 hours of the onset of chest pain. They were 23 men and 3 women, mean age was 59 +/- 8 years. None of them had a history of previous myocardial infarction. From clinical and electrocardiographic data, as well as from creatine kinase curves, we assumed myocardial reperfusion in 19 patients (73%). Within 30' after infusion, thrombin time increased to more than 300" in 25/26 patients (96%). Streptokinase induced hypotension (which we defined as a decrease in systolic blood pressure of more than 30 mmHg) in 13 patients (50%), and in 5 of them (19%) systolic blood pressure fell below 90 mmHg. Hypotension was counteracted by adopting the Trendelenburg position in 7 patients, and by an intravenous infusion of atropine in 5. In the remaining patient, streptokinase infusion was slowed down. Due to these interventions, a non-significant decrease in systolic blood pressure was observed from 129 +/- 26 to 112 +/- 20 mmHg at the end of the infusion. Streptokinase-induced hypotension was not predicted either by clinical, or electrocardiographic, or chest X-ray film data, or laboratory findings. No other side-effects occurred. Hence, the infusion of 1,500,000 streptokinase units in 30' in the acute phase of myocardial infarction is active, and well tolerated. It must be emphasized, however, that during the infusion, hypotension occurs frequently and unpredictably, sometimes reaching alarm levels. This makes the monitoring of systolic blood pressure imperative during streptokinase infusion.

Adult↗
PubMedDate not supplied

Predicting severe ischemic events after uncomplicated myocardial infarction by exercise testing and rest and exercise radionuclide ventriculography.

BACKGROUND: In 183 patients with uncomplicated myocardial infarction, exercise-induced angina, ST segment depression, decrease in ejection fraction, or inadequate increase in systolic blood pressure and low exercise tolerance were significantly associated with 4-year incidence of hard ischemic events. METHODS AND RESULTS: Only the onset of both ST segment depression and a decrease in left ventricular ejection fraction with exercise was an independent predictor. ST segment depression and decrease in left ventricular ejection fraction had low sensitivity (61% and 70%) and specificity (56% and 51%) for hard ischemic events, but specificity increased to 78% when both were present. During medical therapy, 22 of 53 patients with both ST segment depression and a decrease in left ventricular ejection fraction with exercise had an ischemic event (i.e., 48.1% 4-year probability on Kaplan-Meier analysis vs 19.2% in the remaining 130 patients [p < 0.0005]). CONCLUSIONS: Even if no single variable, derived from exercise testing, is a highly sensitive and specific predictor, specificity increases to a clinically relevant level by combining ST segment depression and a decrease in left ventricular ejection fraction with exercise, and in this way patients with recent infarction may be selected for coronary arteriography.

Adult↗