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R Manfredini

Publications and source records attributed to R Manfredini.

At least 19 recordsLinked to original sources
PubMed2007

Transcriptional profiles in melanocytes from clinically unaffected skin distinguish the neoplastic growth pattern in patients with melanoma.

BACKGROUND: It is generally accepted that sunlight may contribute to the development of melanoma. OBJECTIVES: To analyse gene expression of melanocytes obtained from clinically unaffected skin of patients with melanoma and healthy controls before and after exposure to ultraviolet B radiation. METHODS: Using GeneChip array technology, the gene expression of melanocytes obtained from the two donor groups was profiled, in order to identify transcriptional differences affecting susceptibility to melanoma. RESULTS: The data collected did not show any difference between the expression profiles of melanocytes purified from normal donors and from patients with melanoma that was able to give a statistically significant class separation. However, by means of unsupervised clustering our data could be divided into two main classes. The first class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a vertical growth phase (VGP) melanoma, while the second class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a radial growth phase (RGP) melanoma. CONCLUSIONS: These data suggest that melanocytes in patients with VGP and RGP melanomas show significant differences in gene expression profiles, which allow us to classify patients with melanoma also from clinically unaffected skin.

Adult↗
PubMed2006

Exercise capacity and circulating endothelial progenitor cells in hemodialysis patients.

Mobilization of circulating endothelial progenitor cells (EPCs) is increased after acute exercise and training. This study aims to evaluate whether, in a low performance population, EPC levels may be related to exercise capacity in steady state conditions. Study population consisted of sixteen hemodialysis patients. The distance walked in the 6-minute walking test (6 MWD) and the maximal speed attained in an incremental treadmill test were used to assess the exercise capacity. Physical functioning was measured by the scale on the SF36 questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial growth factor receptor-2, were performed. Hemoglobin concentration, white blood cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides were measured. Statistical analysis examined the relationship between blood progenitors cells versus performance parameters, laboratory parameters, age, body mass index, hemodialysis duration, and erythropoietin therapy. Univariate analysis revealed a significant association between percentage values of EPC and performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A similar statistical association between EPC absolute values and performance parameters was found. No correlation between CD34 (+) and any parameter under study was observed. Multivariate analysis indicated 6 MWD as the most significant independent factor associated with EPC level. EPC percentage value was significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the better performing group (6 MWD > 300 m, n=8). In a group of renal patients, mobilization of EPCs was related to the degree of exercise capacity, suggesting a possible connection with the cardiovascular risk in low performance populations limited by chronic diseases.

Aged↗
PubMed2006

Identification of a molecular signature predictive of sensitivity to differentiation induction in acute myeloid leukemia.

Acute myeloid leukemia (AML) blasts are immature committed myeloid cells unable to spontaneously undergo terminal maturation, and characterized by heterogeneous sensitivity to natural differentiation inducers. Here, we show a molecular signature predicting the resistance or sensitivity of six myeloid cell lines to differentiation induced in vitro with retinoic acid or vitamin D. The identified signature was further validated by TaqMan assay for the prediction of response to an in vitro differentiation assay performed on 28 freshly isolated AML blast populations. The TaqMan assay successfully predicts the in vitro resistance or responsiveness of AML blasts to differentiation inducers. Furthermore, performing a meta-analysis of publicly available microarray data sets, we also show the accuracy of our prediction on known phenotypes and suggest that our signature could become useful for the identification of patients eligible for new therapeutic strategies.

Acute Disease↗
PubMed2006

Virally mediated MafB transduction induces the monocyte commitment of human CD34+ hematopoietic stem/progenitor cells.

Upregulation of specific transcription factors is a generally accepted mechanism to explain the commitment of hematopoietic stem cells along precise maturation lineages. Based on this premise, transduction of primary hematopoietic stem/progenitor cells with viral vectors containing the investigated transcription factors appears as a suitable experimental model to identify such regulators. Although MafB transcription factor is believed to play a role in the regulation of monocytic commitment, no demonstration is, to date, available supporting this function in normal human hematopoiesis. To address this issue, we retrovirally transduced cord blood CD34+ hematopoietic progenitors with a MafB cDNA. Immunophenotypic and morphological analysis of transduced cells demonstrated the induction of a remarkable monomacrophage differentiation. Microarray analysis confirmed these findings and disclosed the upregulation of macrophage-related transcription factors belonging to the AP-1, MAF, PPAR and MiT families. Altogether our data allow to conclude that MafB is a key regulator of human monocytopoiesis.

Antigens, CD34↗
PubMed2005

Correlation between differentiation plasticity and mRNA expression profiling of CD34+-derived CD14- and CD14+ human normal myeloid precursors.

In spite of their apparently restricted differentiation potentiality, hematopoietic precursors are plastic cells able to trans-differentiate from a maturation lineage to another. To better characterize this differentiation plasticity, we purified CD14- and CD14+ myeloid precursors generated by 'in vitro' culture of human CD34+ hematopoietic progenitors. Morphological analysis of the investigated cell populations indicated that, as expected, they consisted of granulocyte and monocyte precursors, respectively. Treatment with differentiation inducers revealed that CD14- cells were bipotent granulo-monocyte precursors, while CD14+ cells appeared univocally committed to a terminal macrophage maturation. Flow cytometry analysis demonstrated that the conversion of granulocyte precursors to the mono-macrophage maturation lineage occurs through a differentiation transition in which the granulocyte-related myeloperoxidase enzyme and the monocyte-specific CD14 antigen are co-expressed. Expression profiling evidenced that the observed trans-differentiation process was accompanied by a remarkable upregulation of the monocyte-related MafB transcription factor.

Antigens, CD34↗
PubMed2004

Speed rather than distance: a novel graded treadmill test to assess claudication.

OBJECTIVE: To evaluate a new treadmill test, determining pain threshold speed (PTS) for use in assessment and measuring rehabilitation of patients with intermittent claudication. METHODS AND DESIGN: Twenty-nine patients with claudication were evaluated, and the ankle-brachial index (ABI) was assessed. PTS was determined with a treadmill protocol based on level walking, low starting speed, and progressive increments at a predetermined distance up to the onset of pain. Repeatability and equivalence with a time-based protocol were verified. PTS was compared to pain-free walking distance, 6-minute walking distance, and ABI. RESULTS: PTS was measured in all patients (3.6+/-1.1 km/h). Repeatability and equivalence between established tests were demonstrated. PTS showed a significant correlation with pain-free walking distance (r=0.833; P=0.0001), with 6-minute walking distance (r=0.724; P=0.005), and with ABI in the more ischemic limb (r=0.641; P=0.0001). CONCLUSIONS: PTS is a reliable parameter that correlates well with other established measures. It is useful for determining the degree of functional handicap and for designing and guiding rehabilitation protocols.

Aged↗
PubMed2004

Chronobiology of rupture and dissection of aortic aneurysms.

A growing body of evidence suggests that the occurrence of cardiovascular events is not evenly distributed over time, but shows peculiar temporal patterns that vary with time of day, day of the week, and month (season) of the year. These patterns coincide with the temporal variation in the pathophysiologic mechanisms that trigger cardiovascular events and the physiologic changes in body rhythms. These two factors in combination contribute to the periodicity in susceptibility to acute cardiovascular events. The classic assumption of epidemiologic studies that there is a constancy in risk for disease during the various time domains has now been challenged by the emerging new concept of chronorisk. In the last two decades temporal patterns (circadian, weekly, seasonal) have been identified for several acute cardiovascular diseases, such as acute myocardial infarction, sudden death, pulmonary embolism, and stroke, with peak incidence for most in the morning and during winter. One of the most life-threatening cardiovascular emergencies, aortic aneurysm rupture or dissection, also demonstrates periodicity, characterized by a similar temporal distribution, which suggests a common pathophysiologic mechanism or triggers similar to other cardiovascular acute emergencies. We review the data on chronobiology of acute aortic rupture or dissection, and discuss various pathophysiologic mechanisms that account for this variability. It is likely that identification of consistent recurring patterns in the underlying risk mechanisms could provide potential new insights for more precise diagnosis and efficacious therapeutic intervention.

Aortic Dissection↗
PubMed2004

Risk of hospitalization for upper gastrointestinal tract bleeding.

OBJECTIVE: This study evaluates the hospitalization risk for upper gastrointestinal bleeding (UGIB) with reference to the clinical characteristics of patients and drugs taken before admission. METHODS: This study is based on the GIFA (Italian Group for the Pharmacosurveillance in the Elderly) database. Cases with an ICD-9 code of esophagus, stomach or duodenum bleeding, or acute esophago-gastroduodenal disease associated with anemia have been classified as UGIB. Sex, age, year of observation, drugs taken at home, comorbidity, smoking, alcohol, and use of gastroprotectants have been also taken into account. Statistical analysis has been conducted using multivariate logistic regression models. RESULTS: 32,388 patients have been enrolled, 940 of which presented UGIB. Age, comorbidity, use of smoke and alcohol, hospitalization duration, and mortality during hospitalization were significantly higher in UGIB than nonUGIB patients. Increased UGIB risk has been found in patients taking NSAIDs (both when aspirin was included or excluded), acetaminophen, constipating agents, iron, ethacrynic acid, propranolol. Reduced UGIB risk has been found in patients taking nitrates. CONCLUSIONS: UGIB risk appears to correlate with clinical characteristics of the patient: it increases with age, comorbidity, and smoke and alcohol consumption. Among drugs, NSAIDs are associated with the highest UGIB risk, while nitrates with a reduction of risk.

Aged↗
PubMed2004

Seasonal variation in onset of pulmonary embolism is independent of patients' underlying risk comorbid conditions.

As for many cardiovascular events, pulmonary embolism (PE) is not randomly distributed over time, but shows rhythmic patterns. The purpose of this study was to investigate whether such temporal pattern of occurrence varied in subgroups of patients according to different risk comorbid conditions. All cases of PE observed at the Hospital of Ferrara, Italy, from 1998 to 2001, were considered. After determination of the day of onset, the population was grouped by gender and the most common underlying risk comorbid conditions, e.g., deep vein thrombosis (DVT), neoplasms, cardiomyopathies, traumas/surgical operations, diabetes mellitus, pulmonary diseases, hypertension, cerebrovascular diseases, heart failure, hematologic diseases. For statistical analysis, chi-square test for goodness of fit and partial Fourier series were used. A total of 784 cases (mean age 71 +/- 14 years) were included. Frequency of onset was higher in winter for total population (p = 0.002), men (p = 0.004), DVT (p = 0.001), pulmonary disease (p = 0.008), cardiomyopathies (p = 0.011), and major traumas/surgical operations (p = 0.049). Chronobiologic analysis identified a winter peak for total population (p = 0.008), men (p < 0.001), DVT (p = 0.006), pulmonary diseases (p = 0.017), and hypertension (p = 0.026). This study confirms the winter peak of PE and provides evidence that it is not influenced by the underlying clinical conditions, but probably by endogenous variations.

Aged↗
PubMed2004

Oxidative stress in essential hypertension.

A major cause for endothelial dysfunction in essential hypertension is decreased availability of nitric oxide (NO). Impairment in NO bioavailability is likely to be the consequence of multiple mechanisms affecting NO synthesis as well as NO breakdown. An alteration in the redox balance in endothelial cells leads to increased superoxide anion production and oxidative stress. This in turn not only exerts negative effects on vascular tone, but is also able to activate important mechanisms (such as platelet activity, leukocyte adhesion, vascular smooth muscle cell proliferation and expression of adhesion molecules) with an established central role in the pathogenesis of hypertensive target organ damage. As a consequence, a drug therapy able to restore NO availability in essential hypertensive patients would probably exert additional benefits, as compared to blood pressure lowering per se, in terms of prevention of target organ damage and improved prognosis of these patients. Unfortunately, as of today only the antagonists of the renin-angiotensin system and the calcium-channel blockers have shown some ability in this respect, whereas no longitudinal intervention study has been undertaken, so far, to prove that the restoration of NO bioavailability through an antihypertensive treatment may confer additional prognostic advantage to essential hypertensive patients.

Animals↗
PubMed2004

Training guided by pain threshold speed. Effects of a home-based program on claudication.

AIM: To verify the effectiveness of a 120 day home-based program guided by the pain threshold speed (PTS). METHODS: Twenty-nine patients with stable claudication were measured for ankle pressure (AP), ankle-brachial index (ABI), PTS, maximal speed (Smax) on treadmill. Daily walking sessions at a speed 20-30% below PTS were prescribed. Determination of the training speed was supervised and facilitated at home. The program included a daily record of exercise data and symptoms, an intermediate PTS re-evaluation to adjust the training speed, and the reassessment of all the parameters after 120 days. RESULTS: Overall patients showed a reduction of systemic blood pressure (151.3+/-14.3 to 147.6+/-18.3 mmHg; 77.1 +/-9.1 to 72.4+/-8, p=0.008) while AP did not. ABI increased from 0.65+/-0.13 to 0.71+/- 0.18 (p=0.01). PTS and Smax rose from 3.2+/-1.1 to 4.2+/-1.5 km/h (p=0.0001) and from 3.9+/-1.3 to 4.6+/-1.3 km/h (p=0.0001), respectively. According to their compliance, patients were divided into 3 groups: 1) trained (T, n=14): exercise at the prescribed speed, 2) free-walkers (FW, n=7): walking speed markedly below PTS and 3) untrained (U, n=8): incomplete program compliance. T group showed symptom reduction up to pain disappearance. The ABI change (0.72+/-0.09 to 0.82+/- 0.16, p<0.02) was correlated to AP increase (r= 0.879). PTS and Smax rose from 3.6+/-1.1 to 5.4+/-0.8 km/h (p<0.02) and from 4.7+/-1.2 to 5.7+/-0.7 (p<0.02), respectively. FW showed improvement of all parameters, and U a better walking efficiency. CONCLUSIONS: In patients with claudication, a low-cost home-based program driven by PTS allows dramatic improvements of functional parameters.

Aged↗
PubMed2002

Gene expression profile of Vitamin D3 treated HL60 cells shows an incomplete molecular phenotypic conversion to monocytes.

By high density oligonucleotide microarrays we have studied the expression profile of proliferating and VD treated HL60 cells and the molecular phenotype of VD monocytes and that of CD14+ peripheral monocytes has been compared. The results indicate that important changes in functional categories of the differentially expressed genes underlie the differentiation transition from myeloblasts to monocytes. This differential gene expression pattern leads to an increased expression of mRNAs involved in surface and external activities since many of the VD induced genes belong to ligand binding, receptors, cell surface antigens, defense/immunity and adhesion molecules functional categories. The results also indicate that the molecular phenotypes of monocytes and VD induced cells diverge for a small but significant set of defense related genes. Particularly, class II MHC genes are not expressed in these cells. Furthermore, the high levels of expression of these genes induced by serum treatment of monocytes are decreased by VD.

Cell Differentiation↗
PubMed2002

Competition load and stress in sports: a preliminary study in biathlon.

International sports calendars are being increasingly filled with competitive events and fatiguing travel, at the risk of overloading the athletes involved. The Medical Committee of the International Biathlon Union, in order to check for any significant changes, analysed seven recent competitive seasons, calculating the number of races and total and daily numbers of racing kilometers for each season. A theoretical model for stress was subsequently developed, based on identification and quantification of favourable and unfavourable factors, with establishment of average and maximal stress scores for each season. A questionnaire was distributed to athletes to collect data about daily stress levels, and the correspondence between the theoretical model and the athletes' responses was determined. This analysis demonstrates that the biathlon has become more demanding for those athletes in the racing circuit, with significant increases in number of races, total and daily numbers of kilometers raced, and average stress scores for athletes of both sexes. The self-reported daily stress levels for some athletes show an interesting correspondence with the theoretical stress model. If such correspondence is confirmed, this model might constitute an instrument with which international sports federations, considering the concentration of races, related travel and recovery times, could plan sustainable competitive calendars.

Adult↗