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71.
Long‐term outcome in patients with ST segment elevation myocardial infarction and multivessel disease treated with culprit‐only,immediate, or staged multivessel percutaneous revascularization strategies: Insights from the REAL registry 下载免费PDF全文
72.
A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies 总被引:2,自引:0,他引:2
Perrine SP Hermine O Small T Suarez F O'Reilly R Boulad F Fingeroth J Askin M Levy A Mentzer SJ Di Nicola M Gianni AM Klein C Horwitz S Faller DV 《Blood》2007,109(6):2571-2578
Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type antiviral agents because the viral enzyme target of these antiviral drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently infected B cells. As butyrate has been shown to sensitize EBV(+) lymphoma cells in vitro to apoptosis induced by ganciclovir, arginine butyrate in combination with ganciclovir was administered in 15 patients with refractory EBV(+) lymphoid malignancies to evaluate the drug combination for toxicity, pharmacokinetics, and clinical responses. Ganciclovir was administered twice daily at standard doses, and arginine butyrate was administered by continuous infusion in an intrapatient dose escalation, from 500 mg/(kg/day) escalating to 2000 mg/(kg/day), as tolerated, for a 21-day cycle. The MTD for arginine butyrate in combination with ganciclovir was established as 1000 mg/(kg/day). Ten of 15 patients showed significant antitumor responses, with 4 CRs and 6 PRs within one treatment cycle. Complications from rapid tumor lysis occurred in 3 patients. Reversible somnolence or stupor occurred in 3 patients at arginine butyrate doses of greater than 1000 mg/(kg/day). The combination of arginine butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biologic activity in vivo in EBV(+) lymphoid malignancies which are refractory to other regimens. 相似文献
73.
Laura Annaratone Marco Volante Sofia Asioli Nelson Rangel Gianni Bussolati 《Endocrine pathology》2013,24(2):83-91
The aim of this study was to assess the suitability of using real-time quantitative PCR (RT-qPCR) to characterize neuroendocrine (NE) tumors of the pancreas. For a series of tumors, we evaluated several genes of interest, and the data were matched with the “classical” immunohistochemical (IHC) features. In 21 cases, we extracted RNA from formalin-fixed paraffin-embedded (FFPE) blocks, and in nine cases, we also extracted RNA from fresh-frozen tissue. The RT-qPCR procedure was performed using two sets of customized arrays. The test using the first set, covering 96 genes of interest, was focused on assessing the feasibility of the procedure, and the results were used to select 18 genes indicative of NE differentiation, clinical behavior, and therapeutic responsiveness for use in the second set of arrays. Threshold cycle (Ct) values were used to calculate the fold-changes in gene expression using the 2-??Ct method. Statistical procedures were used to analyze the results, which were matched with the IHC and follow-up data. Material from fresh-frozen samples performed better in terms of the level of amplification, but acceptable and concordant results were also obtained from FFPE samples. In addition, high concordance was observed between the mRNA and protein expression levels of somatostatin receptor type 2A (R?=?0.52, p?=?0.016). Genes associated with NE differentiation, as well as the gastrin-releasing peptide receptor and O-6-methylguanine-DNA methyltransferase genes, were underexpressed, whereas angiogenesis-associated markers (CDH13 and SLIT2) were overexpressed in tissues with malignant behavior. The RT-qPCR procedure is practical and feasible in economic terms for the characterization of NE tumors of the pancreas and can complement morphological and IHC-based evaluations. Thus, the results of the RT-qPCR procedure might offer an objective basis for therapeutic choices. 相似文献
74.
Laura Annaratone Enzo Medico Nelson Rangel Isabella Castellano Caterina Marchiò Anna Sapino Gianni Bussolati 《Endocrine pathology》2014,25(3):219-228
Discordant data are reported in the literature on the definition, incidence and clinical features of neuroendocrine (NE) carcinomas of the breast. This tumour entity is currently assessed by immunohistochemistry (IHC) detecting “general” NE markers such as chromogranin A (CHGA) and synaptophysin (SYP), but other markers have been considered as well. In the present study, in addition to CHGA and SYP, we investigated the expression of VGF, a neurotrophin-inducible gene, which is emerging as a new specific NE marker. In order to evaluate the differential expression of these neuro-endocrine markers in breast cancers, we conducted parallel immunohistochemical and gene expression analyses, using PCR, gene array and real-time quantitative PCR procedures. Data obtained in 28 cases were further validated with a meta-analysis of published datasets of 103 breast cancer cases. The value of IHC positivity (irrespective of the percentage of positive cells) was confirmed by over-expression of the related gene. However, the genetic approach emerged as more sensitive, showing over-expression of NE markers in a subset of IHC-negative carcinomas. In conclusion, the present study confirms, by a novel approach, the occurrence of NE differentiation in breast cancers. Over-expression of one or more NE marker (CHGA and/or SYP and/or VGF) characterizes a significant fraction (approximately 10 %) of infiltrative breast cancers. 相似文献
75.
Benedetta Fibbi Pamela Pinzani Francesca Salvianti Matteo Rossi Luisa Petrone Maria Laura De Feo Roberto Panconesi Vania Vezzosi Simonetta Bianchi Gabriele Simontacchi Monica Mangoni Maurizio Pertici Gianni Forti Cinzia Pupilli 《Endocrine pathology》2014,25(3):324-331
The purpose of this study is to describe a case of concurrent medullary and papillary thyroid carcinoma (MTC and PTC) and cutaneous melanoma and to analyze BRAFV600E mutation in plasma and tissues. We report the clinical history and the laboratory, imaging, and histopathological findings of a 47-year-old man affected by multinodular goiter. BRAFV600E-mutated DNA was quantified in plasma samples and in cancer sections by quantitative real-time polymerase chain reaction (qPCR). At ultrasound examination, the dominant right nodule of the thyroid was weakly hyperechoic and hypervascularized, while the left one was hypoechoic without internal vascularization. Regional lymphadenomegalia was not detected. Basal plasma calcitonin was elevated, and the patient underwent total thyroidectomy and resection of central cervical lymph nodes. Histopathological examination identified two distinct foci of MTC and PTC and micrometastasis of well-differentiated carcinoma in one of the six resected lymph nodes. RET proto-oncogene germline mutations were not detected. Cutaneous melanoma of the thorax was subsequently diagnosed. BRAFV600E tissue DNA was detected in PTC and melanoma but not in MTC. The cell-free plasma percentage of BRAFV600E DNA was detected in pre-thyroidectomy peripheral blood and was drastically reduced after cancer treatments. This study confirms the occurrence of synchronous MTC and PTC and is the first evidence of the co-existence of melanoma and distinct thyroid cancers of different origin. BRAFV600E allele was detected in PTC and melanoma but not in MTC tissues. BRAFV600E molecular quantification in pre- and post-treatment blood supports our previous data, suggesting its possible role in diagnosis and follow-up of BRAF-positive tumors. 相似文献
76.
The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry 下载免费PDF全文
Cocchi F Fusco D Menotti L Gianni T Eisenberg RJ Cohen GH Campadelli-Fiume G 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(19):7445-7450
Entry of herpes simplex virus (HSV) 1 into cells requires the interaction of HSV gD with herpesvirus entry mediator or nectin1 receptors, and fusion with cell membrane mediated by the fusion glycoproteins gB, gH, and gL. We report that the gD ectodomain in soluble form (amino acids 1-305) was sufficient to rescue the infectivity of a gD-null HSV mutant, indicating that gD does not need to be anchored to the virion envelope to mediate entry. Entry mediated by soluble gD required, in addition to the receptor-binding sites contained within residues 1-250, a discrete downstream portion (amino acids 261-305), located proximal to the transmembrane segment in full-length gD. We named it as profusion domain. The pro-fusion domain was required for entry mediated by virion-bound gD, because its substitution with the corresponding region of CD8 failed to complement the infectivity of gD(-/+) HSV. Furthermore, a receptor-negative gD (gD(Delta6-259)) inhibited virus infectivity when coexpressed with wild-type gD; i.e., it acted as a dominant-negative gD mutant. The pro-fusion domain is proline-rich, which is characteristic of regions involved in protein-protein interactions. P291L-P292A substitutions diminished the gD capacity to complement gD(-/+) HSV infectivity. We propose that gD forms a tripartite complex with its receptor and, by way of the proline-rich pro-fusion domain, with the fusion glycoproteins, or with one of them. The tripartite complex would serve to recruit/activate the fusion glycoproteins and bring them from a fusion-inactive to a fusion-active state, such that they execute fusion of the virion envelope with cell membrane. 相似文献
77.
Negro R Formoso G Mangieri T Pezzarossa A Dazzi D Hassan H 《The Journal of clinical endocrinology and metabolism》2006,91(7):2587-2591
CONTEXT: Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications. OBJECTIVE: We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects. DESIGN: This was a prospective study. SETTING: The study was conducted in the Department of Obstetrics and Gynecology. PATIENTS: A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)). INTERVENTION: TPOAb(+) patients were divided into two groups: group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group. MAIN OUTCOME MEASURES: Rates of obstetrical complications in treated and untreated groups were measured. RESULTS: At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7). CONCLUSIONS: Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery. 相似文献
78.
Gianni Misuri Marco Mancini Iacopo Iandelli Roberto Duranti Loredana Stendardi Francesco Gigliotti Elisabetta Rosi Maria Cristina Ronchi Giorgio Scano 《Pulmonary pharmacology & therapeutics》1997,10(5-6)
Whether, and to what extent, β2-agonists protect against respiratory muscle overloading and breathlessness during bronchoconstriction remains to be defined in patients with asthma. In a double blind placebo-controlled study, 100 μg of fenoterol were administered to six stable asthmatics before a bronchial provocation test, performed by inhaling doubling concentrations of histamine from a Devilbiss 646 nebulizer. We recorded breathing pattern (tidal volume VT, inspiratory time TI, total time of the respiratory cycle TTOT), inspiratory capacity (IC), dynamic pleural pressure swing (Pplsw), total lung resistance (RL) and FEV1. VTwas expressed both in actual values and as % of IC. Changes in VT(%IC) during histamine inhalation reflected changes in dynamic end-inspiratory lung volume (EILV). Pplswwas expressed as % of maximal (the most negative in sign) pleural pressure, obtained under control conditions during a sniff manoeuvre (Pplsn). Pplsw(%Pplsn) is an index of inspiratory muscle effort. The test ended when the concentration of histamine which caused a decrease in FEV1of ≥40% post-saline was reached. Dyspnoea rating was scored by a modified Borg scale. At the ultimate degree of bronchoconstriction (UDB) with histamine: (i) decrease in FEV1was similar after placebo and fenoterol, while increase in RLwas lower after fenoterol (P<0.005); (ii) VT(%IC) increased less after fenoterol (P<0.027); (iii) increases in Pplsw(%Pplsn) was lower after fenoterol (P<0.001); (iv) ΔBorg (from saline) was lower (P<0.01) after fenoterol; (v) differences in ΔBorg, from placebo to fenoterol, related to concurrent changes in VT(%IC) (r2=0.67). In conclusion, at UDB 100 μg of fenoterol produced a beneficial effect on the degree of inspiratory muscle loading and breathlessness, an effect greater than it would be expected from measuring FEV1alone. 相似文献
79.
Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors 总被引:12,自引:0,他引:12
Maggioni AP Anand I Gottlieb SO Latini R Tognoni G Cohn JN;Val-HeFT Investigators 《Journal of the American College of Cardiology》2002,40(8):1414-1421
OBJECTIVES: A subgroup analysis of the Valsartan Heart Failure Trial (Val-HeFT) was performed to evaluate the effects of the angiotensin II receptor blocker, valsartan, in the patients with chronic heart failure (HF) not receiving angiotensin-converting enzyme (ACE) inhibitors. BACKGROUND: The ACE inhibitors reduce mortality and morbidity in patients with HF. Nonetheless, nearly 20% of potentially eligible patients may not be prescribed ACE inhibitors. RESULTS: Val-HeFT was an international, randomized, double-blinded trial that compared valsartan with placebo when added to the prescribed treatment of patients with HF. The two primary end points of the study were all-cause mortality and the composite of all-cause mortality and morbidity (sudden death with resuscitation, hospital admission for HF, or administration of intravenous inotropic or vasodilator drugs for >or=4 h without hospital admission). Of the 5,010 patients enrolled in the trial, 366 (7.3%) were not treated with ACE inhibitors at baseline. The effects of valsartan on the primary and secondary end points of the study were assessed in this subgroup of patients. RESULTS: Both all-cause mortality and combined mortality and morbidity for patients not treated with ACE inhibitors were significantly reduced in the valsartan treatment group compared with the placebo group (17.3% vs. 27.1%, p = 0.017 and 24.9% vs. 42.5%, p < 0.001, respectively). Consistent with the data on clinical events, patients randomized to valsartan showed improvements in physiologic variables, such as ejection fraction, left ventricular internal diameter in diastole, and plasma neurohormone levels. Permanent discontinuation of study treatment because of adverse experiences was comparable between the two groups. CONCLUSIONS: Val-HeFT has provided the first placebo-controlled outcome data demonstrating a favorable effect of an angiotensin receptor blocker on mortality and morbidity in patients with HF not treated with ACE inhibitors. Based on these results, valsartan appears to be an effective therapy in ACE inhibitor-intolerant patients. 相似文献
80.
Francesco Zanon Lina Marcantoni Enrico Baracca Gianni Pastore Giuseppina Giau Gianluca Rigatelli Daniela Lanza Claudio Picariello Silvio Aggio Sara Giatti Marco Zuin Loris Roncon Domenico Pacetta Franco Noventa Frits W. Prinzen 《Journal of interventional cardiac electrophysiology》2018,52(1):31-37