Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 31
Filter
1.
Nature ; 591(7848): 54-60, 2021 03.
Article in English | MEDLINE | ID: mdl-33658692

ABSTRACT

Growing interest in quantum computing for practical applications has led to a surge in the availability of programmable machines for executing quantum algorithms1,2. Present-day photonic quantum computers3-7 have been limited either to non-deterministic operation, low photon numbers and rates, or fixed random gate sequences. Here we introduce a full-stack hardware-software system for executing many-photon quantum circuit operations using integrated nanophotonics: a programmable chip, operating at room temperature and interfaced with a fully automated control system. The system enables remote users to execute quantum algorithms that require up to eight modes of strongly squeezed vacuum initialized as two-mode squeezed states in single temporal modes, a fully general and programmable four-mode interferometer, and photon number-resolving readout on all outputs. Detection of multi-photon events with photon numbers and rates exceeding any previous programmable quantum optical demonstration is made possible by strong squeezing and high sampling rates. We verify the non-classicality of the device output, and use the platform to carry out proof-of-principle demonstrations of three quantum algorithms: Gaussian boson sampling, molecular vibronic spectra and graph similarity8. These demonstrations validate the platform as a launchpad for scaling photonic technologies for quantum information processing.

2.
Breast ; 35: 115-121, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28711793

ABSTRACT

BACKGROUND: The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. PATIENTS AND METHODS: This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. RESULTS: From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33-83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1-7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4-58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). CONCLUSIONS: The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.


Subject(s)
Androstadienes/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Everolimus/administration & dosage , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Metastasis , Neoplasm Staging
3.
Int J Food Sci Nutr ; 65(5): 637-45, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24611636

ABSTRACT

This study aims at investigating the effect of an experimental period of intake of whole grain foods rich in lignans as part of an habitual diet on the plasma and urinary excretion of enterolignans, the biomarkers of lipid metabolism and the immunological and antioxidant status in a group of postmenopausal women with moderate serum cholesterol. A randomized double-blind crossover study was completed on 13 subjects in 12-weeks after protocol approval of an ethical committee. The subjects consumed whole grain foods high in lignans (30 g/d of breakfast cereals or biscuits, etc., 80 g/d of whole grain pasta) or refined grain foods for 4 weeks, separated by a 2-weeks wash-out period. A modest hypocholesterolemic effect (p < 0.05) of the whole grain diet was observed and the intake of whole grain products rich in lignans was also associated with an increase in urinary enterodiol excretion (p < 0.05).


Subject(s)
Cholesterol/blood , Edible Grain/chemistry , Lignans/administration & dosage , Postmenopause , Blood Pressure , Body Mass Index , Body Weight , Cross-Over Studies , Diet , Double-Blind Method , Female , Glutathione Peroxidase/blood , Humans , Interleukin-1beta/blood , Interleukin-6/blood , Italy , Lignans/urine , Middle Aged , Pilot Projects , Superoxide Dismutase/blood , Tumor Necrosis Factor-alpha/blood
4.
J Prev Med Hyg ; 53(1): 37-43, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22803318

ABSTRACT

UNLABELLED: INTRODUCTION. The screening programmes are very challenging from the ethical perspective, and their impact in terms of morbidity and mortality make secondary colorectal cancer prevention a valuable public health intervention. METHODS: The target population people aged 50-69 years receive an invitation card with a test-tube for the fecal occult blood test (FOBT) and an immunochemical test is used for fecal occult blood. Subjects positive to FOBT are invited to perform a gastroenterologic examination and a full colonoscopy. RESULTS: In the firt round of screening, 100% of the target population has been invited with an adhesion rate of 41.3%. A total of 1739 FOBT-positive subjects have been invited to the second level of the screening. 1429 of them have performed the gastroenterologic examination (83.9%). To date 956 full colonoscopies have been completed and the rate of subjects affected by carcinoma, malignant polyp and advanced adenoma has been equal to 23.5%. DISCUSSION: Thanks to the reminders already sent, an increasing compliance has been registered with an increased rate of subjects with a low schooling that have performed a FOBT test. With the aim to optimize all the operative aspects of the screening programme it is already ongoing a set of meetings between health workers of Local Health Unit 4 and General Practioners.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Mass Screening/methods , Occult Blood , Patient Acceptance of Health Care/statistics & numerical data , Adenomatous Polyps/diagnosis , Adenomatous Polyps/prevention & control , Aged , Catchment Area, Health , Colonoscopy/statistics & numerical data , Colorectal Neoplasms/epidemiology , Female , Humans , Incidence , Indicators and Reagents , Italy/epidemiology , Male , Middle Aged , National Health Programs/organization & administration , Outcome Assessment, Health Care , Patient Compliance , Prevalence , Reagent Kits, Diagnostic , Sigmoidoscopy/statistics & numerical data
5.
J Intern Med ; 255(3): 399-408, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14871465

ABSTRACT

BACKGROUND: Epidemiological studies have foreseen an increase in the incidence of hepatocellular carcinoma (HCC) in the near future and it is estimated that this trend will mostly affect hepatitis C virus (HCV) positive cirrhotic patients. Therefore, accuracy of HCC staging is an important clinical issue. AIM: To investigate the prognostic usefulness of a series of newly proposed HCC prognostic systems such as the Cancer of the Liver Italian Program (CLIP) score, the Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire (GRETCH) model and the Barcelona Clinic Liver Cancer (BCLC) staging classification when compared with the usefulness of a known staging system such as the Okuda staging system in a group of anti-HCV positive cirrhotic patients with HCC seen at a single centre. METHODS: Okuda stage, CLIP score, GRETCH model and BCLC stages were retrospectively computed in 81 anti-HCV positive cirrhotic patients with HCC. We evaluated and compared the ability of these methods to assess survival prognosis. RESULTS: As of December 2001, 51 patients had died and overall median survival was 18 months. All the staging systems were able to identify various patient subgroups with different survival. The CLIP score, the GRETCH model and the BCLC staging classification were better at characterizing the 1-year prognosis of the patients when compared with the Okuda staging system, whilst the 3-year prognostic evaluation was improved only by using the CLIP score or the BCLC staging classification. CONCLUSIONS: The prognostic value and usefulness of the CLIP score, the GRETCH model and the BCLC staging classification was reproduced in a single-centre analysis of anti-HCV positive HCC cirrhotic patients. These scores provided a prognostic assessment of our patients which is superior to what was obtained by the Okuda staging system.


Subject(s)
Carcinoma, Hepatocellular/pathology , Hepatitis C/complications , Liver Cirrhosis/complications , Liver Neoplasms/pathology , Neoplasm Staging/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/mortality , Female , Hepatitis C/mortality , Hepatitis C/pathology , Humans , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Neoplasms/complications , Liver Neoplasms/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , alpha-Fetoproteins/analysis
6.
Aliment Pharmacol Ther ; 17(12): 1563-9, 2003 Jun 15.
Article in English | MEDLINE | ID: mdl-12823161

ABSTRACT

BACKGROUND: Trans-catheter arterial chemoembolisation (TACE) is the most common palliative treatment for hepatocellular carcinoma (HCC). The therapeutic options depend both on the characteristics of the tumour and on functional staging of the cirrhosis. AIM: To evaluate the effects of TACE on the survival of cirrhotic patients with HCC according to different staging systems [Okuda score, Cancer Liver Italian Program (CLIP) score, Model for End-stage Liver Disease (MELD) score] and in relation to the side-effects of TACE. METHODS: Fifty cirrhotic patients, 36 CTP class A and 14 class B, underwent 106 TACE treatments with mitoxantrone. Survival at 12, 24, and 36 months was evaluated. RESULTS: MELD at 12 months and CLIP at 24 months were identified as significant variables associated with survival. Combined cut-offs of CLIP and of MELD identified four subgroups of patients with different survivals, at 12, 24 and 36 months, respectively: CLIP >or= 2 and MELD >or= 10 (63%, 20% and 0%), CLIP < 2 and MELD >or= 10 (73%, 40% and 22%), CLIP >or= 2 and MELD < 10 (73%, 40% and 22%) and CLIP < 2 and MELD < 10 (100%, 63% and 50%). Post-TACE side-effects proved to have no influence on survival. CONCLUSION: In patients with poor probability of survival (CLIP >or= 2 and MELD >or= 10), TACE must be planned with a great deal of caution, while in patients with possibly good outcomes (CLIP < 2 and MELD < 10), more 'aggressive' therapy should be taken into consideration.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Chemoembolization, Therapeutic/methods , Liver Cirrhosis/virology , Liver Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Liver Failure/etiology , Male , Middle Aged , Neoplasm Staging , Palliative Care , Survival Analysis , Treatment Outcome
7.
Aliment Pharmacol Ther ; 16(4): 717-25, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11929389

ABSTRACT

BACKGROUND: There are few data on the use of the 13C-aminopyrine breath test to evaluate the severity of disease in patients with hepatitis C virus-related chronic liver disease, although these patients represent one of the most important problems in clinical hepatology. AIMS: To compare 13C-aminopyrine breath test results of patients with hepatitis C virus-related chronic hepatitis and Child-Pugh class A cirrhosis with those of normal subjects, and to evaluate different methods of expressing 13C-aminopyrine breath test results. METHODS: Twenty-four patients with hepatitis C virus-related chronic hepatitis and 17 patients with Child-Pugh class A cirrhosis underwent 13C-aminopyrine breath test. Breath samples were collected every 30 min up to 2 h after 13C-aminopyrine administration. 13C-Aminopyrine breath test results were expressed as a percentage of the administered dose of 13C recovered per hour (% dose/h) and the cumulative percentage of administered dose of 13C recovered over time (% dose cum). Nineteen healthy subjects served as controls. Patients with hepatitis C virus-related chronic hepatitis were divided into subgroups on the basis of histological staging and grading. RESULTS: The 13C-aminopyrine breath test result (% dose/h) at 30 min was significantly different among the three subgroups of subjects (normal subjects, 11.5 +/- 3.5; chronic hepatitis patients, 8.1 +/- 4.1; cirrhosis patients, 5.0 +/- 3.1; P < 0.0005). Moreover, the differences between chronic hepatitis and cirrhosis patients were statistically significant (P < 0.03). The fibrosis score showed a significant inverse correlation with the 13C-aminopyrine breath test result (% dose/h) at 30 min (rs=- 0.409, P=0.05). The 13C-aminopyrine breath test result (% dose/h) at 30 min also allowed normal subjects and chronic hepatitis patients with low (< or = 2) or high (> 2) fibrosis scores to be distinguished. The 13C-aminopyrine breath test results (% dose cum) at 30, 60 and 90 min allowed discrimination between normal subjects and chronic hepatitis and cirrhosis patients. The 13C-aminopyrine breath test result (% dose cum) was also able to distinguish between normal subjects and chronic hepatitis patients with high but not low fibrosis scores. Both 13C-aminopyrine breath test results (% dose/h and % dose cum) at 120 min allowed the differentiation between normal subjects and chronic hepatitis patients with high (> or = 6) necro-inflammatory activity. CONCLUSIONS: In patients with hepatitis C virus-related chronic liver disease, the 13C-aminopyrine breath test proved to be safe and easy to perform, and was able to evaluate different degrees of liver function impairment which were partly correlated to clinical and histological evaluation. In future studies, 13C-aminopyrine breath test results should be expressed in a standardized fashion to permit comparison.


Subject(s)
Aminopyrine , Hepatitis C, Chronic/diagnosis , Breath Tests/methods , Carbon Isotopes , Female , Hepatitis C, Chronic/complications , Humans , Liver Cirrhosis/etiology , Male , Middle Aged , Severity of Illness Index
8.
Aliment Pharmacol Ther ; 15(12): 1967-73, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11736728

ABSTRACT

BACKGROUND: Helicobacter pylori gastric infection has been associated with various digestive and extra-digestive diseases. The systemic influence of gastric H. pylori infection seems to be mediated by the release of various cytokines. In liver disease, bacterial infections have been associated with the impairment of liver metabolic function. AIMS: To evaluate the influence of H. pylori infection on liver function as assessed by means of the monoethylglycinexylidide test, which depends upon liver blood flow and cytochrome P-450 activity, and the 13C-galactose breath test, which depends on cytosolic enzymatic activity and is correlated with hepatic functional mass. Moreover, to evaluate whether H. pylori-associated modifications of liver function may be related to tumour necrosis factor-alpha serum levels. PATIENTS AND METHODS: Thirty-five patients with liver cirrhosis of various aetiologies, who underwent monoethylglycinexylidide and 13C-galactose breath tests, were retrospectively evaluated for H. pylori infection by means of anti-H. pylori immunoglobulin G. The main clinical, biochemical and functional characteristics of the patients as well as their tumour necrosis factor-alpha serum levels were then analysed on the basis of the presence of H. pylori infection. RESULTS: Twenty-one patients tested positive for H. pylori infection (60%), and 11 tested negative (31.4%). No clinical or biochemical differences were observed between H. pylori-infected and non-infected patients. H. pylori infection showed no difference in distribution according to Child-Pugh classes (A, 55%; B and C, 67%). The monoethylglycinexylidide test results were significantly lower at each sampling time in H. pylori-positive patients compared to H. pylori-negative patients (MEGX15, P=0.027; MEGX30, P=0.014; MEGX60, P=0.028), while 13C-galactose breath test showed no significant differences considering both cumulative percentage dose and percentage dose/h. The median tumour necrosis factor-alpha serum levels were no different between H. pylori-positive (16.1 pg/mL, 95% confidence interval, 8.7-28.7) and H. pylori-negative (12.3 pg/mL, 95% confidence interval, 8.7-23.4) patients. CONCLUSIONS: In cirrhotic patients, H. pylori infection seems to selectively affect cytochrome P-450 liver activity, while hepatic functional mass does not seem to be impaired. Tumour necrosis factor-alpha does not seem to be the mediator of this impairment. Further studies are needed to evaluate the impact of H. pylori eradication on parameters of liver function.


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Helicobacter Infections/metabolism , Lidocaine/analogs & derivatives , Liver Cirrhosis/metabolism , Liver/metabolism , Aged , Breath Tests , Carbon Radioisotopes , Female , Galactose/metabolism , Helicobacter Infections/immunology , Helicobacter pylori/immunology , Humans , Immunoglobulin G/metabolism , Lidocaine/metabolism , Lidocaine/pharmacology , Liver/immunology , Male , Middle Aged , Retrospective Studies , Tumor Necrosis Factor-alpha/metabolism
9.
Hum Genet ; 109(3): 326-38, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11702214

ABSTRACT

Mutations in the retina-specific ABC transporter (ABCR) gene are responsible for autosomal recessive Stargardt disease (arSTGD). Mutation detection efficiency in ABCR in arSTGD patients ranges between 30% and 66% in previously published studies, because of high allelic heterogeneity and technical limitations of the employed methods. Conditions were developed to screen the ABCR gene by double-gradient denaturing-gradient gel electrophoresis. The efficacy of this method was evaluated by analysis of DNA samples with previously characterized ABCR mutations. This approach was applied to mutation detection in 44 Italian arSTGD patients corresponding to 36 independent genomes, in order to assess the nature and frequency of the ABCR mutations in this ethnic group. In 34 of 36 (94.4%) STGD patients, 37 sequence changes were identified, including 26 missense, six frameshift, three splicing, and two nonsense variations. Among these, 20 had not been previously described. Several polymorphisms were detected in affected individuals and in matched controls. Our findings extend the spectrum of mutations identified in STGD patients and suggest the existence of a subset of molecular defects specific to the Italian population. The identification of at least two disease-associated mutations in four healthy control individuals indicates a higher than expected carrier frequency of variant ABCR alleles in the general population. Genotype-phenotype analysis in our series showed a possible correlation between the nature and location of some mutations and specific ophthalmoscopic features of STGD disease.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Macular Degeneration/genetics , Mutation , ATP-Binding Cassette Transporters/chemistry , Adolescent , Adult , Aged , Alleles , Base Sequence , Case-Control Studies , Child , DNA Mutational Analysis , DNA Primers/genetics , Electrophoresis, Polyacrylamide Gel , Female , Genotype , Humans , Italy , Macular Degeneration/pathology , Male , Middle Aged , Phenotype , Polymorphism, Genetic
10.
Clin Chem ; 47(3): 491-7, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11238302

ABSTRACT

BACKGROUND: Hereditary hyperferritinemia-cataract syndrome is an autosomic dominant disorder caused by heterogeneous mutations on the iron-responsive element (IRE) of ferritin L-chain mRNA. The mutations described to date were identified by direct sequencing of DNA from probands with hyperferritinemia often associated to bilateral cataracts. A direct genetic approach on a large population is useful to recognize polymorphisms in the DNA region and the prevalence of mutations associated with minor increases in serum ferritin and subclinical cataracts. We developed a rapid DNA scanning technique to detect mutations in a single electrophoretic analysis. METHODS: The double-gradient denaturing gradient gel electrophoresis (DG-DGGE) method consisted of PCR amplification of the target genomic DNA with GC-clamped oligonucleotides. The sequence encoded the 5' untranslated flanking region of ferritin L-chain mRNA, which includes an IRE stem-loop structure. The product was subjected to DG-DGGE (8.5-15% polyacrylamide and 50-95% denaturant) to separate the homo- and heteroduplexes. RESULTS: The method clearly identified all eight accessible mutations, including C-G transversions, which are the most difficult to detect. The method was applied to scan DNA samples from 50 healthy subjects and from 230 subjects with serum ferritin >400 microg/L. The new mutation G14C was identified. CONCLUSIONS: The DG-DGGE method detects all the mutations in the L-ferritin IRE sequence, is rapid and economical, and can be applied to scan large populations. The first population study indicated that the mutations are rare and may involve regions of the IRE structure not yet characterized.


Subject(s)
Cataract/genetics , Ferritins/genetics , Hemochromatosis/genetics , Iron/metabolism , Response Elements , Base Sequence , Electrophoresis, Polyacrylamide Gel/methods , Ferritins/blood , Humans , Molecular Sequence Data , Mutation , Polymerase Chain Reaction , Syndrome
12.
Eur J Cardiothorac Surg ; 15(5): 602-7, 1999 May.
Article in English | MEDLINE | ID: mdl-10386404

ABSTRACT

OBJECTIVE: Pulmonary emphysema is frequently associated with lung cancer and, because of the impaired pulmonary function involved, it may contraindicate surgical treatment. However, improvement of pulmonary function has been observed after surgical resection in patients with advanced emphysema. The aim of this study was to evaluate whether pulmonary emphysema, as assessed by pulmonary function tests and radiological evaluation, can influence postoperative respiratory function after lobectomy for non-small cell lung cancer (NSCLC). METHODS: Respiratory function was evaluated before and after lobectomy for NSCLC. Radiological evaluation of emphysema was performed on chest X-ray and CT scan. Patients that had undergone chemo- or radiotherapy or had segmental or lobar atelectasis were excluded from the study. RESULTS: Thirty-five patients entered the study. A decrease in static lung volumes was observed after surgery. Total lung capacity (TLC) decreased from 6.58+/-0.92 to 5.46+/-0.77 l; functional residual capacity (FRC) from 3.70+/-0.88 to 2.96+/-0.73 1 and residual volume (RV) from 2.93+/-0.78 to 2.2+/-0.53 l. However, in a subgroup of 10 patients (Group 1), dynamic volumes after surgery were unchanged or slightly increased (forced vital capacity (FVC) from 3.23+/-0.65 to 3.3+/-0.68 l; forced expiratory volume in 1 s (FEV1) from 2.14+/-0.51 to 2.25+/-0.54 l), and airway resistances (sRaw) decreased from 15.58+/-5.18 to 11.42+/-5.25 cm H2O/s. Preoperative data showed that these patients had a greater obstruction, with FEV1 changing from 69+/-12.42 to 72.70+/-13.72% of predicted, as compared with a change from 87+/-12.7 to 72.08+/-13.10% in the other group of 25 patients (Group 2). Correlation analysis reached statistical significance between FEV1% variation (deltaFEV1%) and preoperative FEV1 and FVC% (r = -0.49, P = 0.002 and r = -0.5, P = 0.001, respectively) and between delta (FEV1)% and radiological scores for 3-level CT (r = 0.39, P = 0.04) and the sum of chest X-ray, single and 3-level CT scores (r = 0.49, P = 0.01). CONCLUSIONS: Pulmonary function may remain unchanged or even increase after lobectomy in patients with a pronounced emphysematous component of airway obstruction. The identification of preoperative parameters that identify this group of patients could extend the indications for the treatment of lung cancer in patients with pulmonary emphysema.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Pneumonectomy/methods , Pulmonary Emphysema/prevention & control , Aged , Carcinoma, Non-Small-Cell Lung/complications , Female , Follow-Up Studies , Humans , Lung Neoplasms/complications , Male , Middle Aged , Postoperative Period , Preoperative Care , Pulmonary Emphysema/diagnosis , Pulmonary Emphysema/etiology , Pulmonary Emphysema/physiopathology , Respiratory Function Tests , Severity of Illness Index , Statistics, Nonparametric , Treatment Outcome
13.
Clin Chem ; 45(1): 35-40, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9895335

ABSTRACT

Among established techniques for the identification of either known or new mutations, denaturing gradient gel electrophoresis (DGGE) is one of the most effective. However, conventional DGGE is affected by major drawbacks that limit its routine application: the different denaturant gradient ranges and migration times required for different DNA fragments. We developed a modified version of DGGE for high-throughput mutational analysis, double gradient DGGE (DG-DGGE), by superimposing a porous gradient over the denaturant gradient, which maintains the zone-sharpening effect even during lengthy analyses. Because of this innovation, DG-DGGE achieves the double goals of retaining full effectiveness in the detection of mutations while allowing identical run time conditions for all fragments analyzed. Here we use retrospective analysis of a large number of well-characterized mutations and polymorphisms, spanning all predicted melting domains and the whole genomic sequence of three different genes--the cystic fibrosis transmembrane conductance regulator (CFTR), the beta-globin, and the p53 genes--to demonstrate that DG-DGGE may be applied to the rapid scanning of any sequence variation.


Subject(s)
DNA Mutational Analysis/methods , DNA/genetics , Electrophoresis/methods , Nucleic Acid Denaturation , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Globins/genetics , Humans , Mutation , Polymorphism, Genetic , Reproducibility of Results , Tumor Suppressor Protein p53/genetics
14.
Clin Chem Lab Med ; 36(12): 959-61, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9915229

ABSTRACT

Denaturing gradient gel electrophoresis displays the highest detection rate among mutation scanning methods. In classical denaturing gradient gel electrophoresis the denaturant gradient range and migration times vary for every amplicon to be scanned, greatly affecting the routine application of the method. As an alternative, we developed double gradient denaturing gradient gel electrophoresis where a gradient of pore size is superimposed over the denaturing one, allowing maintenance of the zone-sharpening effect even over prolonged time runs, and adoption of identical run time conditions for all fragments analyzed. Here double gradient denaturing gradient gel electrophoresis has been applied to the analysis of a number of point mutations and polymorphisms located in several exons of three different genes, the cystic fibrosis transmembrane conductance regulator, the beta-globin and the p53 genes.


Subject(s)
DNA/genetics , Electrophoresis, Polyacrylamide Gel/methods , Point Mutation , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Genes, p53 , Globins/genetics , Humans
16.
Pharmacol Biochem Behav ; 56(3): 499-505, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9077589

ABSTRACT

The present study evaluates the influence of cholera toxin and its B-subunit on thermic responses to morphine in the rats. The holotoxin (1 microg/rat) and the B-subunit (5 microg) were administered ICV and three days later rats were challenged ICV with morphine and tested for changes of body temperature. Cholera toxin, but not its B-subunit, modified the time course of the hyperthermic response induced by a low dose of morphine (2.5 microg), converted the hypothermia due to a higher dose of morphine (18 microg) to a consistent hyperthermia and only partially reduced the greater hypothermia induced by 36 microg of morphine. Cholera toxin-induced modifications of thermic responses to morphine were paralleled with a decreased Gs(alpha) immunoreactivity and a reduced ability for the toxin to catalyse the "in vitro" ADP-ribosylation of Gs(alpha) in hypothalamic membranes. In contrast, at the same time when morphine-induced effects on body temperature were assessed, no changes in pertussis toxin-mediated ADP-ribosylation of Gi(alpha)/Go(alpha), or basal adenylate cyclase activity, or binding of mu-opioid receptor selective ligand [3H]-DAMGO were observed in hypothalamic areas from rats treated with cholera toxin. These findings suggest that adaptative events secondary to prolonged activation of Gs(alpha) play a role in the modifications of thermic responses to morphine induced by CTX.


Subject(s)
Analgesics, Opioid/pharmacology , Body Temperature Regulation/drug effects , Cholera Toxin/pharmacology , Morphine/pharmacology , Adenosine Diphosphate Ribose/metabolism , Adenylyl Cyclases/drug effects , Animals , Catalysis , Drug Evaluation, Preclinical , Female , GTP-Binding Proteins/metabolism , Injections, Intraventricular , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/drug effects
17.
Acta Otorhinolaryngol Ital ; 14(1): 41-57, 1994.
Article in Italian | MEDLINE | ID: mdl-8036888

ABSTRACT

After discussing histogenetic, morphologic and evolutive aspects that distinguish haemangiomas from vascular malformations, the Authors affirm the important role that haemodynamic stimuli take on in the evolution of the latter. Vascular malformations are subdivided into capillary, venous and arterial, according to where they originate in the vascular tree. With reference to haemangiomas, the Authors underline the importance of steroid therapy and the necessity to resort to integrative surgical procedure in those cases which do not respond satisfactorily to steroid therapy. The different procedures to be performed, according to dimension and localization of the haemangiomas, are explained in detail. In capillary vascular malformations of small significance from a haemodynamic and evolutionary point of view, comparable to a slightly pathological capillary network, the surgeon often faces complex reconstructive problems which involve, however, only the tegument. These can be resolved using forehead flaps, if necessary, expanded. Arteriovenous vascular malformations are more problematic and therefore require greater surgical skill, prone as they are to progressive expansion and aggravation brought about by haemodynamic mechanisms.


Subject(s)
Arteriovenous Malformations/surgery , Hemangioma/surgery , Nose Neoplasms/surgery , Angiography , Arteriovenous Malformations/diagnosis , Diagnosis, Differential , Embolization, Therapeutic , Hemangioma/diagnosis , Humans , Preoperative Care , Sclerotherapy
18.
Eur J Pharmacol ; 222(2-3): 241-5, 1992 Nov 10.
Article in English | MEDLINE | ID: mdl-1451736

ABSTRACT

The influence of pertussis toxin (PTX) on thermic responses elicited by morphine and neurotensin was evaluated in unrestrained rats kept at 22 degrees C. High doses of morphine (9-36 micrograms/rat i.c.v.) lowered body temperature and low doses (1.25, 2.5 micrograms/rat i.c.v.) produced hyperthermia. The hyperthermic effect was more resistant than the hypothermic effect to naloxone antagonism. Neurotensin (50, 100 micrograms/rat i.c.v.) induced marked hypothermia followed by hyperthermia. I.c.v. injection of PTX (1 microgram), six days before morphine (18 micrograms/rat i.c.v.), replaced the opiate hypothermia by consistent hyperthermia and reduced by 60% the hyperthermia elicited by morphine (2.5 micrograms/rat i.c.v.). The toxin also affected the thermic responses induced by neurotensin (50 micrograms/rat i.c.v.) administered six days after PTX (1 microgram/rat i.c.v.). The initial hypothermia was enhanced by 173% and the late hyperthermia was fully antagonized. It thus appears that PTX-sensitive G-proteins play different roles in the molecular events underlying the thermoregulatory responses to morphine and neurotensin.


Subject(s)
Body Temperature/drug effects , Morphine/pharmacology , Neurotensin/pharmacology , Pertussis Toxin , Virulence Factors, Bordetella/pharmacology , Animals , Drug Interactions , Female , Injections, Intraventricular , Rats , Rats, Sprague-Dawley
19.
Eur J Clin Chem Clin Biochem ; 30(7): 439-44, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1381966

ABSTRACT

The clinical validity of a continuous colorimetric method for measuring pancreatic lipase was assessed. 1,2-Diacylglycerol containing long-chain fatty acid residues was used as substrate, and the method was adapted to a discrete analyser. The dynamic range was ascertained up to at least 30-fold the upper reference limit. Precision tests on three control sera yielded overall CVs of 4.6% (mean value 21 U/l), 2.4% (115 U/l), and 1.0% (386 U/l), respectively. Using serum samples from normal subjects and patients with pancreatic and non-pancreatic disorders, the present method was compared with a turbidimetric method (r = 0.997; n = 281) and a homogeneous enzyme immunoassay (r = 0.987; n = 93). The reference interval established on 121 healthy subjects was 8-57 U/l (central 95th percentile, median 22 U/l). The sensitivity of this lipase assay in the diagnosis of acute pancreatitis (100%, median 5.6-fold the upper reference limit) was equal to that of the pancreatic isoamylase assay, and higher than that of the total alpha-amylase assay (88.2%); the specificity for acute pancreatitis with respect to a group of patients with acute and chronic non-pancreatic abdominal diseases (91%) was higher than that of both pancreatic isoamylase (76%) and total alpha-amylase (71%).


Subject(s)
Clinical Enzyme Tests/methods , Colorimetry/methods , Lipase/blood , Acute Disease , Amylases/blood , Carcinoma/diagnosis , Chronic Disease , Female , Humans , Isoamylase/blood , Male , Pancreatic Neoplasms/diagnosis , Pancreatitis/diagnosis , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Stomach Diseases/diagnosis , Substrate Specificity
20.
J Anim Sci ; 67(12): 3397-409, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2613585

ABSTRACT

To evaluate the effect of zeranol implants in steers on compensatory ++growth, 80 steer calves (9 mo of age; 200 kg) were fed at two feeding levels (RO = 9.2 MJ ME/kg DM; R1 = 6.9 MJ ME/kg DM) for 119 d (Period 1). During Period 2, steers were full-fed to 400 kg BW with (Z1) or without (ZO) zeranol implants. Ten steers were slaughtered at the end of Period 1 to estimate carcass composition. Differences of 100 kg in BW were achieved by restriction in Period 1. Subsequent to restriction, cumulative ADG remained greater (P less than .05) up to the 24th wk of recuperation and implants increased (P less than .001) BW gain by 31% and 24% for RO and R1, respectively. The average daily energy intake (ME/W(.75) in Period 2 was similar for all treatments. Feed conversion was improved by 21.5% (P less than .05) by implants. At the end of Period 2 the R1ZO had 8.6 kg less muscle (P less than .001), 2.9 kg less bone (P less than .001) and 5.9 kg more fat (P less than .05) than the ROZO. In comparison, the carcasses of the implanted animals did not show significant differences (P greater than .05) due to restriction. Carcass daily gains were increased by previous restriction (P less than .01) and implants (P less than .05). Zeranol increased daily live weight gain and feed conversion in animals in continuous growth as well as in those observed in compensatory growth an tended to eliminate a tendency for higher content of fat in carcasses of nonimplanted animals making compensatory growth.


Subject(s)
Cattle/growth & development , Eating/drug effects , Resorcinols/pharmacology , Zeranol/pharmacology , Animals , Body Composition/drug effects , Drug Implants , Male , Random Allocation , Weight Gain/drug effects , Zeranol/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL
...