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Biomedical subjects

P Forte

Publications and source records attributed to P Forte.

At least 19 recordsLinked to original sources
PubMed2005

Recent developments in durum wheat chromosome engineering.

Transfer of alien chromosome segments from various Triticeae species into cultivated wheats, commonly referred to as "chromosome engineering", is currently benefiting from the recent, impressive advancements in molecular genetics, cytogenetics and genomics, which are providing new insights into the genetic and physical organization of even complex plant genomes, such as those of the Triticeae. The powerful analytical tools presently available are making the assessment of desired genotypes in the course of chromosome engineering far more precise and effective than in the past, thus giving this transfer strategy renewed and increased potential for meaningful practical achievements. Examples are given here of the application of such tools to the engineering of the durum wheat genome with small alien segments containing genes with beneficial impact on disease resistance and quality traits.

Chromosomes, Plant↗
PubMed2005

Brain natriuretic peptide and acute coronary syndrome.

The natriuretic peptide system (atrial natriuretic peptide, brain natriuretic peptide, BNP, and C natriuretic peptide) is an important marker of cardiac failure. These peptides are synthesized in atrial or ventricular myocytes in response to wall tension. In several studies the correlation between high BNP levels and mortality, in patients with acute coronary syndrome and heart failure, has been demonstrated. On the other hand, plasma levels of BNP could be considered as independent predictors of mortality in patients with heart failure. BNP could be used, for instance, as an early diagnostic marker for the differential diagnosis between cardiogenic and non cardiogenic dyspnea. In the Emergency Department its use will be important in the diagnosis of thoracic pain origin since it may help in the diagnostic and therapeutic course of this patient and to define the modality of hospitalization. Moreover, it can be used as a marker of heart failure severity and as an important negative prognostic factor. Some studies have confirmed that plasma BNP reflects the degree of left ventricular dysfunction and the prognostic significance after acute myocardial infarction and chronic heart failure.

Angina, Unstable↗
PubMed2005

Heart failure and therapy.

The clinical syndrome of heart failure is the final outcome of a number of diseases affecting the heart. Several studies undertaken over the past decade, have led to a significant change in the therapies available and a growing understanding of the physiopathological mechanisms. Increasingly, the current treatment of heart failure, is not just symptomatic but also etiologic and physiopathologic. In this paper we will try to furnish guidelines, as practical as possible, for the treatment of this syndrome, addressing the physiopathologic and experimental principles which underlie it. The present suggestions are based on the updated literature review, they conform to the latest guidelines of the European Society of Cardiology and are in agreement with the classification in grades, proposed by the American Heart Association and the American College of Cardiology.

Heart Failure↗
PubMed2005

Review of dilated cardiomyopathies. Dilated cardiomyopathies and altered prothrombotic state: a point of view of the literature.

Heart failure is an enormously important clinical problem that, if not faced, may overwhelm health care resources. Primary and secondary cardiomyopathies cause the majority of cases of clinical heart failure, which is thus better approached from the utility point of view of myocardial failure. Furthermore, the risk of thromboembolic complications presenting in such disease may be higher than in ischemic cardiomyopathy. Intracardiac thrombi and mural endocardial plaques (from the organization of thrombi) are present at necropsy in more than 50% of patients with dilated cardiomyopathy (DCM). Several studies have shown that systemic and pulmonary emboli are more frequent in patients with ventricular thrombi or plaques. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. Platelet activation, thrombin activation and fibrinolytic activity are increased in patients with DCM compared to normal subjects. However, these markers reflecting coagulation activation in patients with left ventricle thrombus are comparable to those in patients without thrombus in the left ventricle. The pathophysiology and clinical issues concerning the susceptibility to develop left ventricular (LV) thrombosis and its complications like cerebrovascular disease in patients with DCM are summarized and the most recent articles present in the medical literature are reviewed.

Animals↗
PubMed2004

[Usefulness of magnetic resonance imaging for the diagnosis of acute myocarditis. A case of acute myocarditis as myocardial infarction-like].

According to the Dallas criteria, myocarditis is defined histologically as an inflammatory process involving the myocardium with an inflammatory infiltrate and myocyte necrosis or damage. Clinically, myocarditis is an insidious disease that is usually asymptomatic and commonly underdiagnosed. Infact, the symptoms are often non-specific and the majority of cases recover fully with no sequelae. At present, endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis, despite its limited sensitivity and specificity. However, the lack of an association between biopsy evidence of myocarditis and the presence of autoantibodies in patients with clinical signs of myocarditis, the paucity of the positive biopsy findings in large cohorts of patients with suspected myocarditis, the potential discordance between clinical and histologic features and the inherent limitation of histologic diagnosis, suggest that the diagnosis shouldn't be based on histologic examination alone. The magnetic resonance imaging (MRI) with gadolinium can be useful to visualize the localization, activity and extent of inflammation and may be a powerful noninvasive diagnostic tool in acute myocarditis. Infact, MRI achieves a 100% sensitivity and a 90% specificity. We report the case of a 31-year-old male patient with an acute myocarditis with electrocardiographic manifestations like to acute myocardial infarction, whose diagnosis was based on the clinical signs and on the characteristic pattern of the MRI with paramagnetic contrast. The MRI with gadolinium is suggested as noninvasive study to support the diagnosis of acute myocarditis in the correct clinical setting.

Acute Disease↗
PubMed2003

[Humoral and cellular inflammatory mediators in acute lung injury: friends or enemies? ].

Diffuse lung injury (DLI) is characterised by damage to the alveolar and endothelial epithelium that leads to acute respiratory insufficiency. From the histological point of view, this pathological process proceeds through an initial exudative phase which is followed by the organisation of the inflammatory infiltrate up to the deposit of collagen and fibrin which seriously compromises gaseous exchanges. The clinical expression typical of this pathology consists of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) characterised by hypoxemia resistant to oxygen therapy, tachypnea and the presence of bilateral infiltrates on conventional X-ray of the thorax. Although the etiology is multifactorial, the pathogenesis depends on the uncontrolled activation of the inflammation system in its humoral and cellular components. The present paper examines the principal studies regarding the most important mediators. From an analysis of the literature it emerges that some cytokines (IL-1betha, IL-6, IL-6ra) and cellular mediators (NF-kB, sFasL) are responsible for the epithelial damage by way of complex mechanisms that include apoptosis. Studies carried out up to the present have not however evidenced any independent pathway decisive for pathogenesis. This shows that inflammation is in effect a multiform process that originates precisely as a result of the mutual interaction of the factors implicated in it. The humoral and cell mediators can, however, be used as clinical indicators correlatable with the clinical and physiopathological outcome.

Antibody Formation↗
PubMed2001

HLA-G inhibits rolling adhesion of activated human NK cells on porcine endothelial cells.

Human NK cells adhere to and lyse porcine endothelial cells (pEC) and therefore may contribute to the cell-mediated rejection of vascularized pig-to-human xenografts. Since MHC class I molecules inhibit the cytotoxic activity of NK cells, the expression of HLA genes in pEC has been proposed as a potential solution to overcome NK cell-mediated xenogeneic cytotoxicity. HLA-G, a minimally polymorphic HLA class I molecule that can inhibit a wide range of NK cells, is an especially attractive candidate for this purpose. In this study we tested whether the expression of HLA-G on pEC inhibits the molecular mechanisms that lead to adhesion of human NK cells to pEC and subsequent xenogeneic NK cytotoxicity. To this end two immortalized pEC lines (2A2 and PED) were stably transfected with HLA-G1. Rolling adhesion of activated human NK cells to pEC monolayers and xenogeneic cytotoxicity against pEC mediated by polyclonal human NK lines as well as NK clones were inhibited by the expression of HLA-G. The adhesion was partially reversed by masking HLA-G on pEC with anti-HLA mAbs or by masking the HLA-G-specific inhibitory receptor ILT-2 on NK cells with the mAb HP-F1. The inhibition of NK cytotoxicity by HLA-G was only partially mediated by ILT-2, indicating a role for other unknown NK receptors. In conclusion, transgenic expression of HLA-G may be useful to prevent human NK cell responses to porcine xenografts, but is probably not sufficient on its own. Moreover, the blocking of rolling adhesion by HLA-G provides evidence for a novel biological function of HLA molecules.

Animals↗
PubMed2000

Porcine aortic endothelial cells transfected with HLA-G are partially protected from xenogeneic human NK cytotoxicity.

In this study we tested whether the expression of HLA-G protects porcine endothelial cells (PEC) from the lysis mediated by human natural killer (NK) cells. Because HLA-E is not present in PEC, this model provides an ideal tool to study the direct role of HLA-G in NK inhibition. Immortalized porcine aortic endothelial cells (PED) were stably transfected with a vector coding for the HLA-G1 protein and surface expression was demonstrated by flow cytometry analysis. Although the adhesion of human NK cells to PED was not compromised by HLA-G, the expression of HLA-G partially protected PED from the lysis mediated by polyclonal NK lines derived from different donors. A decrease of the surface expression of HLA-G on PED corresponded to a loss of the capacity of PED to inhibit NK cytotoxicity, indicating that the surface density of HLA-G molecules must exceed a certain threshold to protect target cells. In summary, these data show that HLA-G, independent from the presence of HLA-E, can only partially and inefficiently protect PED from human NK cell-mediated cytotoxicity. Because ILT-2/LIR-1 expression did not correlate with HLA-G mediated inhibition, we hypothesize that other yet unidentified receptors expressed by peripheral blood NK cells are involved in the recognition of HLA-G.

Animals↗
PubMed2000

Nitric oxide synthesis and isoprostane production in subjects with type 1 diabetes and normal urinary albumin excretion.

The role of nitric oxide (NO) and free radicals in the development of microvascular disease in type 1 diabetes remains unclear. We have measured NO and isoprostane (a stable marker of in vivo lipid peroxidation) production in 13 type 1 diabetic subjects with normal urinary albumin excretion and 13 healthy volunteers. Whole-body NO synthesis was quantified by measuring the urinary excretion of 15N-nitrate after the intravenous administration of L-[15N]2-arginine. The urinary excretion of the major urinary metabolite of 15-F2t-isoprostane (8-iso-prostaglandin-F2alpha), 2,3-dinor-5,6-dihydro-F2t-IsoP, was quantified as a marker of in vivo lipid peroxidation. Whole-body NO synthesis was significantly higher in diabetic subjects compared with control subjects (342 vs. 216 nmol 15N-nitrate/mmol creatinine [95% CI of the difference 45-207], P = 0.005). This increase was not explained by a difference in renal function between the 2 groups. There was no difference in 2,3-dinor-5,6-dihydro-F2t-IsoP excretion between diabetic subjects and control subjects (44.8+/-7.8 vs. 41.4+/-10.0 ng/mmol creatinine, mean +/- 95% CI). However, there was an inverse correlation between NO synthesis and free radical activity in subjects with diabetes (r = -0.62, P = 0.012) that was not observed in control subjects (r = 0.37, P = 0.107). We conclude that whole-body NO synthesis is higher in type 1 diabetic subjects with normal urinary albumin excretion than in control subjects. The inverse correlation between isoprostane production and NO synthesis in diabetic subjects is consistent with the hypothesis that NO is being inactivated by reactive oxygen species.

Adult↗
PubMed1999

Nitric oxide synthesis in patients with infective gastroenteritis.

BACKGROUND: There is evidence that endogenous nitrate synthesis is notably increased in patients with infective gastroenteritis. AIMS: To determine whether this is due to nitric oxide (NO) production via the L-arginine/NO pathway. METHODS: Seven male patients with community acquired bacterial gastroenteritis and 15 healthy male volunteers participated in this study. All patients had stool culture positive infective gastroenteritis. A bolus of 200 mg L-[(15)N](2)-arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours. Urinary [(15)N:(14)N]nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. RESULTS: Mean 36 hour total urinary nitrate excretion in the gastroenteritis group was 5157 (577) micromol compared with 2594 (234) micromol in the control group (p<0.001). Thirty six hour urinary [(15)N]nitrate excretion was considerably higher in the gastroenteritis group compared with the control group (13782 (1665) versus 1698 (98) etamol; p<0.001). These values represent 1.129 (0.139)% and 0.138 (0.007)% of [(15)N]nitrogen administered (p<0.001), respectively. Corrected 36 hour urinary [(15)N]nitrate excretion for urinary creatinine was also significantly higher in the patient compared with the control group (1934 (221) versus 303 (35) etamol/mmol; p<0.001). CONCLUSION: Results show notably enhanced nitrate synthesis due to increased activity of the L-arginine/NO pathway in patients with infective gastroenteritis.

Adult↗
PubMed1998

Evidence for a difference in nitric oxide biosynthesis between healthy women and men.

There is indirect evidence for a gender difference in nitric oxide (NO) synthesis from vascular endothelium. The aim of the present study was to determine NO production more directly in healthy women and men by the measurement of 15N nitrate excreted in urine after the intravenous administration of L-[15N]2-guanidino arginine. Twenty-four healthy volunteers (13 men aged 22 to 40 years and 11 women aged 23 to 42 years) participated in this study. No subjects were receiving any medication. Women were studied between the 7th and 14th days of their menstrual cycles. Arterial blood pressure was measured oscillometrically, and 1.13 micromol L-[15N]2 arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours in separate 12-hour periods. Urinary 15N/14N nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. Mean 36-hour urinary 15N nitrate excretion was greater in women than in men (2111+/-139 versus 1682+/-87 etamol; P<0.05). Furthermore, total urinary 15N nitrate excretion was associated inversely with the mean arterial blood pressure in the whole group of subjects (coefficient of correlation, 0.47; P=0.022). The present data show that whole-body production of NO is greater in healthy premenopausal women than in men under ambulatory conditions. The cellular origin of NO measured in this study is unknown, but differences in endothelial production could underlie differences in vascular function between men and women.

Adult↗
PubMed1997

Basal nitric oxide synthesis in essential hypertension.

BACKGROUND: There is indirect evidence that nitric oxide (NO) synthesis in vascular endothelium of patients with hypertension is altered. The aim of this study was to estimate more directly NO production in patients with untreated essential hypertension by measurement of synthesis of inorganic nitrate, which is the end product of NO oxidation in humans. Two separate studies were undertaken in patients with hypertension and appropriate healthy controls. METHODS: In the first study, ten patients and 13 controls were given a diet containing 82 mumoles nitrate per day for 2 days, with urinary and plasma nitrate measurement and 24 h ambulatory blood pressure monitoring on the 2nd day. In the second study, 11 patients and 11 controls were studied in the postabsorptive state; a bolus of 200 mg L[15N]2 arginine was administered intravenously over 10 min. 24 h ambulatory blood pressure monitoring was done and complete urine collections were made for the next 36 h. FINDINGS: In the first study, 24 h urinary nitrate excretion was lower in the hypertensive patients than in the control group (mean 450 [SEM 37] vs 760 mumoles [77] per 24 h; p < 0.001). There was an inverse correlation between average mean daytime ambulatory blood pressure and nitrate excretion (p = 0.007; r2 = -0.73). In the second study, mean 36 h urinary 15N nitrate excretion was significantly lower in the hypertensive than in the control group (1313 [50] vs 2133 [142] pmoles; p < 0.001). There was an inverse correlation also between average mean daytime ambulatory blood pressure and 24 h urinary 15N nitrate excretion expressed per mmole of creatinine (p = 0.002, r2 = -0.59). In addition, total urinary 15N nitrate excretion in the hypertensive group was significantly higher in women than in men (285 [16] vs 198 [14] micrograms 15N nitrate per kg; p = 0.026). INTERPRETATION: These data suggest that whole-body NO production in patients with essential hypertension is diminished under basal conditions. The origin of the NO we measured is not known, and we cannot tell whether the impaired synthesis is primary or secondary to a rise in blood pressure.

Adult↗
PubMed1997

Induction of CD4+ T cell depletion in mice doubly transgenic for HIV gp120 and human CD4.

It has been suggested that loss of uninfected T cells in HIV infection occurs because of lymphocyte activation resulting in cell death by apoptosis. To address the question of whether cross-linking of CD4/HIV gp120 complexes by antibodies were sufficient to induce T cell depletion in vivo, we developed an animal model of continuous interaction between human CD4 (hCD4), gp120 and anti-gp120 antibodies in the absence of other viral factors. Double-transgenic mice have been generated in which T cells express on their membrane hCD4 and secrete HIV gp120. Although these mice have hCD4/gp120 complexes present on the surface of T cells, they do not show gross immunological abnormalities, and they are able to produce anti-gp120 antibodies following immunization with denaturated gp120. However, double-transgenic mice with antibodies to gp120, when immunized with tetanus toxoid, mount an IgG response that is significantly lower than that of double-transgenic mice without antibodies to gp120. Furthermore, the presence of anti-gp120 antibodies leads to CD4+ T cell depletion and immunodeficiency in the absence of HIV infection. Thus, the antibody response to gp120 can lead to CD4+ T cell attrition in vivo.

Animals↗