Search PubMed⌕ Search

Biomedical subjects

Giuseppe D'Onofrio

Publications and source records attributed to Giuseppe D'Onofrio.

10 recordsLinked to original sources
PubMed2006

Lower hemoglobin levels in human immunodeficiency virus-infected patients with a positive direct antiglobulin test (DAT): relationship with DAT strength and clinical stages.

BACKGROUND: There are conflicting opinions regarding the effect of positive direct antiglobulin test (DAT) on hemoglobin (Hb) levels in human immunodeficiency virus-infected (HIV+) patients. STUDY DESIGN AND METHODS: A total of 166 samples from HIV+ outpatients were studied. The DAT was performed with the tube test and column agglutination technology (CAT). RESULTS: The DAT was positive in 18.67 percent with the tube method and 33.73 percent with the CAT. Patients with DAT-positive results showed lower Hb levels than DAT-negative patients, 12.3 g per dL versus 14.3 g per dL (p = 0.0002). The univariate logistic regression enabled us to study the phenomenon better and fit the probability of having a DAT-positive result on the basis of the Hb levels. The relationship between the CAT and the tube test when washing the red blood cells (RBC) at 4 degrees C was stronger than when washing these at room temperature (phi = 0.8156; p = 0.000). The Hb levels were significantly lower in the positive DATs of Stage C (acquired immune deficiency syndrome [AIDS]) and Stage B (symptomatic non-AIDS patients), which showed decreasing Hb values for increasing agglutination strengths (p = 0.000). Anemia was related with the DAT results (odds ratio [OR], 8.005; p = 0.000) but not to the AIDS condition (OR, 1.741; p = 0.221). DISCUSSION: Our study indicates that the DAT-positive results may be specifically related to lower Hb levels in HIV+ patients. The immunologic RBC clearance could be part of the anemic multifactorial condition in HIV+ patients.

Anemia↗
PubMed2005

Persistent systemic inflammation in unstable angina is largely unrelated to the atherothrombotic burden.

OBJECTIVES: The aim of this study was to assess the relationship between systemic inflammation, atherosclerosis, and thrombosis in two distinct clinical models of atherothrombosis. BACKGROUND: Persistent unstable angina (UA) is commonly associated with coronary thrombosis and persistent systemic inflammation. METHODS: We assessed circulating markers of activation of the thrombotic and fibrinolytic cascades and systemic soluble and cellular markers of inflammation on admission in 40 patients with persisting UA (Braunwald class IIIB; group 1) and 30 patients with Leriche-Fontaine stage IIB-III peripheral artery disease awaiting revascularization (group 2). RESULTS: The extent of atherosclerosis (p < 0.01) and activation of the coagulation system were greater in group 2, which had higher thrombin-antithrombin III complexes and D-dimer levels (2.7 and 24.4 microg/l, respectively), than in group 1 (2.0 microg/l and 12.9 microg/l, p = 0.02 and p = 0.0001, respectively). In contrast, C-reactive protein and interleukin-6 levels were higher in group 1 (7.6 pg/ml and 7.8 pg/ml, respectively) than in group 2 (4.5 pg/ml and 3.0 pg/ml, p < 0.01 and p = 0.03, respectively). Moreover, neutrophil activation was only found in group 1 (neutrophil myeloperoxidase content -4.0 arbitrary units vs. +3.4 arbitrary units in group 2, p < 0.0001). These differences persisted during the initial three days of hospitalization. CONCLUSIONS: Such a large, consistent discrepancy between atherothrombotic burden and systemic inflammation suggests that atherothrombosis, by itself, is an unlikely cause of persisting, recurring UA. An understanding of the primary inflammatory mechanisms of persistent and recurrent coronary instability could open the way to novel therapeutic strategies.

Aged↗
PubMed2005

The compositional transition of vertebrate genomes: an analysis of the secondary structure of the proteins encoded by human genes.

Fluctuations and increments of both C(3) and G(3) levels along the human coding sequences were investigated comparing two sets of Xenopus/human orthologous genes. The first set of genes shows minor differences of the GC(3) levels, the second shows considerable increments of the GC(3) levels in the human genes. In both data sets, the fluctuations of C(3) and G(3) levels along the coding sequences correlated with the secondary structures of the encoded proteins. The human genes that underwent the compositional transition showed a different increment of the C(3) and G(3) levels within and among the structural units of the proteins. The relative synonymous codon usage (RSCU) of several amino acids were also affected during the compositional transition, showing that there exists a correlation between RSCU and protein secondary structures in human genes. The importance of natural selection for the formation of isochore organization of the human genome has been discussed on the basis of these results.

Animals↗
PubMed2004

Base composition and expression level of human genes.

It is well known that the gene distribution is non-uniform in the human genome, reaching the highest concentration in the GC-rich isochores. Also the amino acid frequencies, and the hydrophobicity, of the corresponding encoded proteins are affected by the high GC level of the genes localized in the GC-rich isochores. It was hypothesized that the gene expression level as well is higher in GC-rich compared to GC-poor isochores [Mol. Biol. Evol. 10 (1993) 186]. Several features of human genes and proteins, namely expression level, coding and non-coding lengths, and hydrophobicity were investigated in the present paper. The results support the hypothesis reported above, since all the parameters so far studied converge to the same conclusion, that the average expression level of the GC-rich genes is significantly higher than that of the GC-poor genes.

Base Composition↗
PubMed2003

LDH-A and alpha-actin as tools to assess the effects of temperature on the vertebrate genome: some problems.

In a recent paper written with the purpose of shedding light on the question of whether genomic GC levels are related to temperature in vertebrates, Ream et al. [Mol. Biol. Evol. 20 (2003) 105] offered an analysis of two sets of homologous genes: those coding for alpha-actin and lactate dehydrogenase-A (LDH-A). The conclusion was that "there is no consistent relationship between adaptation temperature and the percentage of thermal stability-enhancing G+C base pairs in protein-coding genes". We argue here that the data presented neither prove nor suggest such a conclusion because of conceptual and methodological errors.

Actins↗
PubMed2003

Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis.

BACKGROUND AND OBJECTIVES: Glutamine (gln), a non-essential amino acid, has recently received increasing attention because it becomes essential during stress and catabolic states: glutamine seems to modulate immune function and to promote faster intestinal healing after chemotherapy. We designed two consecutive randomized clinical trials to evaluate the role of glutamine-enriched parenteral nutrition (GEPN) in patients with hematologic malignancies submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation (aPBSCT) or immunoselected CD34+ aPBSCT. DESIGN AND METHODS: In study1, the Gln group (12 patients) received total parenteral nutrition (TPN) enriched with glutamine 20 g from day +1 after aPBSCT, while the placebo group (15 patients) received TPN lacking in glutamine (placebo). In study2, the Gln group (10 patients) received TPN enriched with glutamine 13.46 g from day +1, while the placebo group (11 patients) received a placebo. RESULTS: In the first study, a lymphocyte count >0.5 109/L was achieved on day 16.5 in the Gln group and on day 29 in the placebo group (p=0.005); in the second study, the lymphocyte count >0.5 109/L was achieved on day 18 in the Gln group and on day 29 in the placebo group (p=0.009). Lymphocyte subset analysis showed an increase of CD3+ and CD4+ and normalization of the CD16+CD56+ subset. Furthermore patients receiving GEPN showed a decrease in the mucositis severity peak calculated by the DMS (daily mucositis score: sum of the daily score of signs and symptoms) (p=0.047). INTERPRETATION AND CONCLUSIONS: GEPN is safe and effective and improves lymphocyte recovery after aPBSCT; further studies are needed to assess the clinical benefits of such an approach in order to justify its economic impact.

Adolescent↗
PubMed2002

The base composition of the genes is correlated with the secondary structures of the encoded proteins.

The analysis of a non-redundant set of human proteins, for which both the crystallographic structures and the corresponding gene sequences are available, show that bases at third codon position are non-uniformly distributed along the coding sequences. Significant compositional differences are found by comparing the gene regions corresponding to the different secondary structures of the proteins. Inter-and intra-structure differences were most pronounced in the GC-richest genes. These results are not compatible with any proposed hypotheses based on a neutral process of formation/maintenance of the high GC(3) levels of the genes localized in the GC-richest isochores of the human genome.

Amino Acids↗
PubMed2002

Expression patterns and gene distribution in the human genome.

Genes are non-uniformly distributed in the human genome, reaching the highest concentration in GC-rich isochores. This is one of the fundamental aspects of the human genome organization (Gene 241/259 (2000a,b) 3/31, for a review). In the present paper the gene distribution was analyzed in relationship to the gene expression pattern and levels. In this study evidence is produced showing: (i) that a biased gene distribution towards GC-rich isochores applies to both tissue-specific and housekeeping genes; and (ii) that genes localized in GC-rich isochores have high transcriptional levels. Since gene density and transcriptional levels are correlated with each other and both are correlated with the GC content of the isochores, the biased gene distribution in the human genome presumably is the result of selection at the gene expression levels.

Base Composition↗
PubMed2002

Widespread coronary inflammation in unstable angina.

BACKGROUND: Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. In unstable angina, activated leukocytes may be found in peripheral and coronary-sinus blood, but it is unclear whether they are selectively activated in the vascular bed of the culprit stenosis. METHODS: We measured the content neutrophil myeloperoxidase content in the cardiac and femoral circulations in five groups of patients: two groups with unstable angina and stenosis in either the left anterior descending coronary artery (24 patients) or the right coronary artery (9 patients); 13 with chronic stable angina; 13 with variant angina and recurrent ischemia; and 6 controls. Blood samples were taken from the aorta, the femoral vein, and the great cardiac vein, which selectively drains blood from the left but not the right coronary artery. RESULTS: The neutrophil myeloperoxidase content of aortic blood was similar in both groups of patients with unstable angina (-3.9 and -5.5, with negative values representing depletion of the enzyme due to neutrophil activation) and significantly lower than in the other three groups (P<0.05). Independently of the site of the stenosis, the neutrophil myeloperoxidase content in blood from the great cardiac vein was significantly decreased in both groups of patients with unstable angina (-6.4 in those with a left coronary lesion and -6.6 in those with a right coronary lesion), but not in patients with stable angina and multiple stenoses, patients with variant angina and recurrent ischemia, or controls. There was also a significant transcoronary reduction in myeloperoxidase content in both groups with unstable angina. CONCLUSIONS: The widespread activation of neutrophils across the coronary vascular bed in patients with unstable angina, regardless of the location of the culprit stenosis, challenges the concept of a single vulnerable plaque in unstable coronary syndromes.

Aged↗