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Find video protocols related to scientific articles indexed in Pubmed.
Detection of monoclonal T populations in patients with KIR-restricted chronic lymphoproliferative disorder of NK cells.
Haematologica
PUBLISHED: 09-05-2014
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The etiology of chronic large granular lymphocyte proliferations, either T or Natural Killer, is largely unknown. Although these disorders are characterized by the expansion of different cells types (T and Natural Killer) with specific genetic features and abnormalities, several lines of evidence suggest a common pathogenetic mechanism. According to this interpretation, we speculated that in patients with Natural Killer-type Chronic lymphoproliferative Disorder, together with Natural Killer cells, also T lymphocytes should undergo a persistent antigenic pressure, possibly resulting in an ultimate clonal T cell selection. To strengthen this hypothesis, we evaluated whether clonal T cell populations were detectable in 48 patients with Killer Immunoglobulin-like Receptor restricted Natural Killer-type Chronic lymphoproliferative Disorder. At the time of diagnosis, in a half of patients studied, we found a clearly defined clonal T cell population, despite the fact that all cases presented with a well characterized Natural Killer disorder. Follow up analysis confirmed that TCR gamma rearrangements were stable over the time; furthermore, in seven patients we demonstrated the appearance of a clonal T subset which progressively grows up, leading to a switch between Killer Immunoglobulin-like Receptor restricted Natural Killer-type Disorder to a monoclonal T Large Leukemia. Results of this study support the hypothesis that a common mechanism is involved in the pathogenesis of these disorders.
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Should Thiazide Diuretics be Given as First Line Antihypertensive Therapy or in Addition to Other Medications?
High Blood Press Cardiovasc Prev
PUBLISHED: 04-24-2014
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The recommendation to start antihypertensive therapy with diuretics (D) might produce delay in blood pressure (BP) control and, possibly, increase cost/benefit ratio.
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Leukaemic cells from chronic lymphocytic leukaemia patients undergo apoptosis following microtubule depolymerization and Lyn inhibition by nocodazole.
Br. J. Haematol.
PUBLISHED: 03-07-2014
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Functional abnormalities of chronic lymphocytic leukaemia (CLL) cells may be related to the microtubular network of cell cytoskeleton; specifically tubulin involvement in cells after B-cell receptor engagement. As microtubule inhibitors could represent a therapeutic strategy for CLL, this study investigated the capability of nocodazole, a synthetic depolymerizing agent, to kill CLL leukaemic cells. We demonstrated that nocodazole was highly specific for the in vitro induction of apoptosis in leukaemic cells from 90 CLL patients, without affecting the viability of T-cells and/or mesenchymal stromal cells (MSCs) recovered from the same patients. Nocodazole was observed to overcome the pro-survival signals provided by MSCs. Competing with ATP for the nucleotide-binding site, nocodazole has been observed to turn off the high basal tyrosine phosphorylation of leukaemic cells mediated by the Src-kinase Lyn. Considering that most anti-microtubule drugs have limited clinical use because of their strong toxic effects, the high selectivity of nocodazole for leukaemic cells in CLL and its capability to bypass microenvironmental pro-survival stimuli, suggests the use of this inhibitor for designing new therapeutic strategies in CLL treatment.
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Cortactin, another player in the Lyn signaling pathway, is over-expressed and alternatively spliced in leukemic cells from patients with B-cell chronic lymphocytic leukemia.
Haematologica
PUBLISHED: 02-14-2014
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Cortactin, an actin binding protein and Lyn substrate, is up-regulated in several cancers and its level is associated with increased cell migration, metastasis and poor prognosis. The identification that the Src kinase Lyn and its substrate HS1 are over-expressed in B-cell chronic lymphocytic leukemia and involved in resistance to chemotherapy and poor prognosis, prompted us to investigate the role of cortactin, an HS1 homolog, in the pathogenesis and progression of this disorder. In this study, we observed that cortactin is over-expressed in leukemic cells of patients (1.10 ± 0.12) with respect to normal B lymphocytes (0.19 ± 0.06; P=0.0065). Fifty-three percent of our patients expressed the WT mRNA and p80/85 protein isoforms, usually lacking in normal B lymphocytes which express the SV1 variant and the p70/75 protein isoforms. Moreover, we found an association of the cortactin overexpression and negative prognostic factors, including ZAP-70 (P<0.01), CD38 (P<0.01) and somatic hypermutations in the immunoglobulin heavy-chain variable region (P<0.01). Our results show that patients with B-cell chronic lymphocytic leukemia express high levels of cortactin with a particular overexpression of the WT isoform that is lacking in normal B cells, and a correlation to poor prognosis, suggesting that this protein could be relevant in the pathogenesis and aggressiveness of the disease.
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Lyn-mediated procaspase 8 dimerization blocks apoptotic signaling in B-cell chronic lymphocytic leukemia.
Blood
PUBLISHED: 12-18-2013
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Lyn, a member of the group of tyrosine kinases named the Src family kinases (SFKs), is over-expressed, associated with an aberrant multiprotein complex and constitutively active in B-cell chronic lymphocytic leukemia (B-CLL) cells, resulting in a high level of tyrosine phosphorylation and contributing to their resistance to apoptosis. By using biochemical and bioinformatics tools, we identified procaspase-8, the caspase-8 zymogen, as a cytosolic target for Lyn in B-CLL cells, the phosphorylation of which at Tyr380 promotes the formation of an inactive procaspase-8 homodimer. This complex remains segregated in the cytosol and appears to be crucial in mediating the anti-apoptotic function of Lyn in this disease. The significance of the Lyn-procaspase-8 axis in impairing apoptosis in B-CLL cells was further confirmed by pharmacological and genetic inhibition of procaspase-8, which drastically reduced the apoptosis induced by the SFK inhibitors PP2 and dasatinib. Our data highlight that Lyns dysregulated expression, activity and localization in B-CLL supports resistance to cell demise by inhibiting an early player of apoptotic signaling, potentially broadening the perspectives of developing new strategies for the treatment of this disease.
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Hypertensive target organ damage predicts incident diabetes mellitus.
Eur. Heart J.
PUBLISHED: 07-23-2013
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Whether patients with hypertensive preclinical cardiovascular disease (CVD) are at higher risk of incident diabetes has never been studied.
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Resveratrol improves vascular function in patients with hypertension and dyslipidemia by modulating NO metabolism.
Hypertension
PUBLISHED: 06-10-2013
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Epidemiological studies have demonstrated that the Mediterranean diet, which is rich in resveratrol, is associated with a significantly reduced risk of cardiovascular disease. However, the molecular mechanisms that underlie the beneficial effects of resveratrol on cardiovascular function remain incompletely understood. Therefore, we set out to identify the molecular target(s) mediating the protective action of resveratrol on vascular function. To this end, we performed vascular reactivity studies to evaluate the effects of resveratrol on superior thyroid artery obtained from 59 patients with hypertension and dyslipidemia. We found that resveratrol evoked vasorelaxation and reduced endothelial dysfunction through the modulation of NO metabolism via (1) an 5 adenosine monophosphate-activated protein kinase-mediated increase in endothelial NO synthase activity; (2) a rise in tetrahydrobiopterin levels, which also increases endothelial NO synthase activity; and (3) attenuation of vascular oxidative stress, brought about by overexpression of manganese superoxide dismutase via an nuclear factor erythroid-derived 2-like 2-dependent mechanism. The effects of resveratrol on acetylcholine vasorelaxation were also tested in vessels from patients with nonhypertensive nondyslipidemia undergoing thyroid surgery. In this setting, resveratrol failed to exert any effect. Thus, our finding that resveratrol reduces endothelial dysfunction, an early pathophysiological feature and independent predictor of poor prognosis in most forms of cardiovascular disease, supports the concept that the risk of vascular events could be further reduced by adherence to a set of dietary and behavioral guidelines.
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Antihypertensive response to combination of olmesartan and amlodipine does not depend on method and time of drug administration.
High Blood Press Cardiovasc Prev
PUBLISHED: 05-09-2013
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Fixed combinations of antihypertensive drugs have the potentiality to improve blood pressure (BP) control. However, when pharmacokinetic parameters of the two drugs are different, both method and time of administration of the two drugs may modify the antihypertensive response. In an open-label, single-blind, randomized study we compared antihypertensive effect of four administration schemes of a combination therapy of olmesartan and amlodipine in the same group of hypertensive patients, using ambulatory blood pressure monitoring (ABPM). The olmesartan + amlodipine combination has demonstrated to provide a good control of BP, with systolic and diastolic BP constantly below 130 and 85 mmHg over the 24 h. The simultaneous or separate administration of the 2 drugs fully overlapped, suggesting that the fixed combination and the separate administration induce a similar and sustained BP control.
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Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases.
Food Chem. Toxicol.
PUBLISHED: 04-23-2013
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Resveratrol-a natural polyphenolic compound-was first discovered in the 1940s. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. A large part of these effects are related to its antioxidant properties. Here we review: (a) the sources, the metabolism, and the bioavailability of resveratrol; (b) the ability of resveratrol to modulate redox signalling and to interact with multiple molecular targets of diverse intracellular pathways; (c) its protective effects against oxidative damage in cardio-cerebro-vascular districts and metabolic disorders such as diabetes; and (d) the evidence for its efficacy and toxicity in humans. The overall aim of this review is to discuss the frontiers in the field of resveratrols mechanisms, bioactivity, biology, and healthrelated use.
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Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia.
Blood
PUBLISHED: 03-20-2013
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The JAK/STAT pathway is altered in T-cell large granular lymphocytic leukemia. In all patients, leukemic LGLs display upregulation of phosphorylated STAT3 (P-STAT3) that activates expression of many antiapoptotic genes. To investigate the mechanisms maintaining STAT3 aberrantly phosphorylated using transcriptional protein and functional assays, we analyzed interleukin (IL)-6 and suppressor of cytokine signaling-3 (SOCS3), 2 key factors of the JAK/STAT pathway that induce and inhibit STAT3 activation, respectively. We showed that IL-6 was highly expressed and released by the patients peripheral blood LGL-depleted population, accounting for a trans-signaling process. By neutralizing IL-6 or its specific receptor with specific antibodies, a significant reduction of P-STAT3 levels and, consequently, LGL survival was demonstrated. In addition, we found that SOCS3 was down-modulated in LGL and unresponsive to IL-6 stimulation. By treating neoplastic LGLs with a demethylating agent, IL-6-mediated SOCS3 expression was restored with consequent P-STAT3 and myeloid cell leukemia-1 down-modulation. Methylation in the SOCS3 promoter was not detectable, suggesting that an epigenetic inhibition mechanism occurs at a different site. Our data indicate that loss of the inhibitor SOCS3 cooperates with IL-6 to maintain JAK/STAT pathway activation, thus contributing to leukemic LGL survival, and suggest a role of demethylating agents in the treatment of this disorder.
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Assessment of the 9p21.3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes.
BMC Med. Genet.
PUBLISHED: 01-23-2013
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The 9p21.3 locus is strongly associated with the risk of coronary artery disease (CAD) and with type 2 diabetes (T2D). We investigated the association of 9p21.3 variants with severity of CAD (defined by the number of vessel diseased [VD]) in the presence and absence of T2D.
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Smoking selectively accelerates carotid atherosclerosis in hypertensive patients.
High Blood Press Cardiovasc Prev
PUBLISHED: 01-22-2013
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Background and objectives: Left ventricular hypertrophy, carotid atherosclerosis and renal dysfunction are indicators of target organ damage in hypertension, and independent risk factors for both fatal and non-fatal cardio- and cerebrovascular events. In the general population, smoking is associated with increases in left ventricular mass and carotid intima-media thickness (IMT), and impaired renal function. The aim of the present study was to evaluate whether smoking affects the development of target organ damage in patients with arterial hypertension. Methods: 3192 hypertensive patients referred to the Hypertension Clinic of the "Federico II" University of Naples from January 2000 to July 2006 were retrospectively analysed. Subjects were aged from 18 to 75 years. Among these patients, 1391 were smokers and 1801 non-smokers. Results: The duration and severity of hypertension was significantly shorter in smokers when compared with non-smokers. The maximum arterial IMT was significantly higher in smokers compared with non-smokers (1.7 ± 0.1 mm vs 1.5 ± 0.1, p < 0.0001), while left ventricular mass index was comparable between the two groups. In contrast, glomerular filtration rate was observed to be higher in smokers compared with non-smokers. Logistic regression analysis showed that smoking, age, sex, duration of hypertension, systolic blood pressure and diastolic blood pressure were significantly correlated with IMT. Furthermore, a strong correlation was found between the number of cigarettes smoked per day and IMT. Conclusions: Together, these data indicate that in hypertensive patients who have a high risk of developing atherosclerosis, smoking could potentiate the development of atherosclerotic plaques.
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Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia.
Am. J. Hematol.
PUBLISHED: 01-07-2013
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The immunoglobulin heavy chain variable (IGHV) gene mutational status represents a major prognostic marker in chronic lymphocytic leukemia (CLL). Usually, the prognostic implications of IGHV gene analysis can be reliably ascertained but, occasionally, double productive rearrangements have been detected. Clinical presentation and biological features of such cases are unknown. Sixty patients with morphologically and phenotypically monoclonal CLL but double productive IGHV rearrangements were retrospectively identified by mRNA analysis from three Hematology Institutions. Clinical and biological features and survival of these 60 patients were compared with a control group of patients with CLL and single IGHV rearrangement. A prospective registry was used to assess the epidemiology of double productive IGHV among incidental patients with CLL. Using standard criteria to define IGHV-mutated (M) or unmutated (U) cases, 39 of the 60 patients (65%) with double productive IGHV rearrangement had concordant status (23 MM, 16 UU), while 21 (35%) had discordant IGHV status. As compared with M patients, the MM ones had lower CD38 expression, more favorable cytogenetics and more indolent clinical behavior. Cases with UU had similar characteristics of U patients. Discordant cases presented with adverse prognostic features and had an aggressive clinical behavior requiring early treatment, similar to U patients. The prevalence of double IGHV was 3.1%. Patients with CLL with double concordant mutational status (MM or UU) have a clinical course similar to that of the corresponding single IGHV status, while those exhibiting discordant status represent a high risk population. This may help correct stratification within clinical trials.
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Effects of nutraceuticals on prevalence of metabolic syndrome and on calculated Framingham Risk Score in individuals with dyslipidemia.
J. Hypertens.
PUBLISHED: 05-26-2010
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Nutraceuticals (NUTs) are forms of compounds with biological activity and are used to improve health in dosage largely exceeding those obtainable in food.
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The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events.
BMC Cardiovasc Disord
PUBLISHED: 02-26-2010
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The clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis.
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Cross-talk between PKA and Akt protects endothelial cells from apoptosis in the late ischemic preconditioning.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 05-21-2009
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The aim of this study was to explore the molecular mechanisms involved in late preconditioning-induced cell protection in endothelial cells.
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Insufficient control of blood pressure and incident diabetes.
Diabetes Care
PUBLISHED: 02-17-2009
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Incidence of type 2 diabetes might be associated with preexisting hypertension. There is no information on whether incident diabetes is predicted by blood pressure control. We evaluated the hazard of diabetes in relation to blood pressure control in treated hypertensive patients.
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Effects of particulate matter (PM(10), PM(2.5) and PM(1)) on the cardiovascular system.
Toxicology
PUBLISHED: 01-16-2009
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Several studies have demonstrated that exposure to particulate matter (PM) of different size fractions is associated with an increased risk of cardiovascular disease (CVD). In this review, we have taken into consideration the possible correlation between the "short term" and "long term" effects of PM exposure and the onset of CVDs as well as the possible molecular mechanisms by which PM elicits the development of these events. Particularly, it is here underlined that these adverse health effects depend not only on the level of PM concentration in the air but also on its particular internal composition. Furthermore, we have also synthesized the findings gleaned from those few studies indicating that PM produced by tobacco smoke can give rise to cardiovascular injury.
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Statins and the elderly: recent evidence and current indications.
Aging Clin Exp Res
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Cardiovascular disease (CVD) is estimated to remain as the main cause of death in developed nations over the next 30 years, with increased prevalence in the older population. This is because the observed decline in the incidence of CVD owing to improvements in prevention has now been counterbalanced by the increased shift toward an older and thus more fragile population. Statin treatment reduces cardiovascular morbidity and mortality in middle-aged adults. However, few studies have included older individuals, particularly those aged 80 years or over. The adverse effects associated with high doses of statins and their interactions with other drugs may give rise to more problems in the elderly population. Evidence remains limited regarding the overall benefit of starting statin therapy in adults aged 80 and over; so that clinical judgment remains necessary in making the decision to use them. In this review, we present available evidence from randomized clinical trials, as well as relative community and post-approval data directly applicable to the management of CVD in the elderly, in both primary and secondary prevention. Also discussed is the latest evidence regarding the putative protective effects of statins on senile dementia and the relationship between statin treatment and cancer.
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Nutraceuticals for blood pressure control in patients with high-normal or grade 1 hypertension.
High Blood Press Cardiovasc Prev
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Current hypertension management guidelines do not recommend drug treatment in subjects with blood pressure (BP) in the high-normal range due to the risk of side effects of the currently available antihypertensive agents that overcomes the possible benefit. Nutraceuticals are free from relevant side effects and could be a valuable strategy for the treatment of these patients.
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Variant on chromosome 9p is associated with left ventricular mass: results from two cohorts of essential hypertensive individuals.
J. Hypertens.
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It is well known that among hypertensive patients, an increased left ventricular mass (LVM) is a powerful predictor of cardiovascular morbidity and mortality. However, the mechanisms underlying LVM in hypertension are not completely understood, as the absolute value of blood pressure and other risk factors associated do not predict alone a definite LVM progression. Recently, the 9p21 chromosomal region has been consistently associated with coronary heart disease.
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Lifestyle-related risk factors, smoking status and cardiovascular disease.
High Blood Press Cardiovasc Prev
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Cardiovascular disease represents one of the most important causes of morbidity and mortality in highly developed countries and is known to be associated with some lifestyle-related risk factors (e.g. alcohol consumption, smoking status, diet, physical activity, bodyweight). There is still incomplete information about their combined effect on cardiovascular risk in hypertensive patients with optimal pharmacological blood pressure control.
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HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
PLoS ONE
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In B-Chronic Lymphocytic Leukemia (B-CLL) kinase Lyn is overexpressed, active, abnormally distributed, and part of a cytosolic complex involving hematopoietic lineage cell-specific protein 1 (HS1). These aberrant properties of Lyn could partially explain leukemic cells defective apoptosis, directly or through its substrates, for example, HS1 that has been associated to apoptosis in different cell types. To verify the hypothesis of HS1 involvement in Lyn-mediated leukemic cell survival, we investigated HS1 protein in 71 untreated B-CLL patients and 26 healthy controls. We found HS1 overexpressed in leukemic as compared to normal B lymphocytes (1.38±0.54 vs 0.86±0.29, p<0.01), and when HS1 levels were correlated to clinical parameters we found a higher expression of HS1 in poor-prognosis patients. Moreover, HS1 levels significantly decreased in ex vivo leukemic cells of patients responding to a fludarabine-containing regimen. We also observed that HS1 is partially localized in the nucleus of neoplastic B cells. All these data add new information on HS1 study, hypothesizing a pivotal role of HS1 in Lyn-mediated modulation of leukemic cells survival and focusing, one more time, the attention on the BCR-Lyn axis as a putative target for new therapeutic strategies in this disorder.
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Persistence and adherence to antihypertensive treatment in relation to initial prescription: diuretics versus other classes of antihypertensive drugs.
J. Hypertens.
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The use of thiazide diuretics in the treatment of hypertension is widely considered as a first-line treatment, given the efficacy and low cost of this class of drugs. This indication is not unanimous, because thiazides can cause metabolic alterations, and other side effects that reduce compliance and persistence on treatment.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.