| 1. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 2. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 3. |
- Chakera, Annette H., et al.
(författare)
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EANM-EORTC general recommendations for sentinel node diagnostics in melanoma
- 2009
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:10, s. 1713-1742
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Forskningsöversikt (refereegranskat)abstract
- The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, ( 8) use of dye, ( 9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.
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| 4. |
- Padeletti, Luigi, et al.
(författare)
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Duration of P-wave is associated with atrial fibrillation hospitalizations in patients with atrial fibrillation and paced for bradycardia
- 2007
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Ingår i: PACE. - : Wiley. - 1540-8159. ; 30:8, s. 961-969
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Tidskriftsartikel (refereegranskat)abstract
- Background: A trial fibrillation (AF) is a common problem in pacemaker patients. We conducted a prospective observational study in patients paced for bradycardia with associated paroxysmal or persistent AF, to determine whether P-wave duration may stratify patients at higher risk for AF recurrences and AF-related hospitalizations. The patients were evaluated for the prevalence, cause, and predictors of hospitalization. Methods: We studied 660 consecutive patients (50% male, 72 +/- 9 years) who received a dual-chamber pacemaker. Median value of baseline P-wave duration was equal to 100 ms (25%-75% quartile range equal to 80-120 ms). We used this cut-off to divide the patients into group A (P <= 100 ms), composed of 385 (58.3%) patients, and group B (P > 100 ms), composed of 275 (41.7%) patients. Results: In a median follow-up of 19 months, 173 patients were hospitalized for all causes, 130 for cardiovascular causes, and 85 for AF-related hospitalizations. Multivariate logistic analysis showed that P-wave duration > 100 ms identified patients at higher risk (OR = 1.6, 95% confidence interval (1.1-2.8), P = 0.044) for AF-related hospitalizations. Patients in group B (P > 100 ms) more frequently suffered AF-related hospitalizations (16.4% vs 10.4%, P = 0.02) and underwent more frequent cardioversions (14.5% vs 9.1%, P = 0.029) compared with group A (P < 100 ms). Conclusions: P-wave duration may define the risk of persistent AFrequiring cardioversion or AF-related hospitalization in patients with a pacemaker for bradycardia with associated paroxysmal or persistent AF.
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| 5. |
- Viale, Giuseppe, et al.
(författare)
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Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole.
- 2008
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 26:34, s. 5569-75
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. PATIENTS AND METHODS: Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. RESULTS: Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). CONCLUSION: Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.
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| 6. |
- Bertuccio, Giuseppe, et al.
(författare)
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Ultra Low Noise Epitaxial 4H-SiC X-Ray Detectors
- 2009
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Ingår i: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 615-617, s. 845-848
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Tidskriftsartikel (refereegranskat)abstract
- The design and the experimental results of some prototypes of SiC X-ray detectors are presented. The devices have been manufactured on top of 2 inch 4H-SiC wafer with 115 μm thick undoped high purity epitaxial layer, which constitutes the detection’s active volume. Pad and pixel detectors based on Ni-Schottky junctions have been tested. The residual doping of the epi-layer was found tobe extremely low, 3.7 x 1013 cm-3, allowing to achieve the highest detection efficiency and the lower specific capacitance of the detectors. At 22 °C and in operating bias condition, the reverse current densities of the detector’s Schottky junctions have been measured to be between J = 0.3 pA/cm2 and J = 4 pA/cm2; these values are more than two orders of magnitude lower than those of state of the art silicon detectors. With such low leakage currents, the equivalent electronic noise of SiC pixel detectors is as low as 0.5 electrons r.m.s at room temperature, which represents a new state of the art in the scenario of semiconductor radiation detectors.
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| 7. |
- Bomben, Riccardo, et al.
(författare)
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Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia : an Italian multicenter study
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 109:7, s. 2989-2998
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Tidskriftsartikel (refereegranskat)abstract
- IGHV3-21-using chronic lymphocytic leukemia (CLL) is a distinct entity with restricted immunoglobulin gene features and poor prognosis and is more frequently encountered in Northern than Southern Europe. To further investigate this subset and its geographic distribution in the context of a country (Italy) with both continental and Mediterranean areas, 37 IGHV3-21 CLLs were collected out of 1076 cases enrolled by different institutions from Northern or Central Southern Italy. Of the 37 cases, 18 were identified as homologous (hom)HCDR3-IGHV3-21 CLLs and were found almost exclusively (16 of 18) in Northern Italy; in contrast, 19 nonhomHCDR3-IGHV3-21 cases were evenly distributed throughout Italy. Clinically, poor survivals were documented for IGHV3-21 CLLs as well as for subgroups of mutated and homHCDR3-IGHV3-21 CLLs. Negative prognosticators CD38, ZAP-70, CD49d, and CD79b were expressed at higher levels in homHCDR3 than nonhomHCDR3-IGHV3-21 cases. Differential gene expression profiling (GEP) of 13 IGHV3-21 versus 52 non-IGHV3-21 CLLs identified, among 122 best-correlated genes, TGFB2 and VIPR1 as down- and up-regulated in IGHV3-21 CLL cases, respectively. Moreover, GEP of 7 homHCDR3 versus 6 nonhomHCDR3-IGHV3-21 CLLs yielded 20 differentially expressed genes, with WNT-16 being that expressed at the highest levels in homHCDR3-IGHV3-21 CLLs. Altogether, IGHV3-21 CLLs, including those with homHCDR3, had a peculiar global phenotype in part explaining their worse clinical outcome.
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| 8. |
- Cardaropoli, Giuseppe, 1968, et al.
(författare)
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Healing of extraction sockets and surgically produced - augmented and non-augmented - defects in the alveolar ridge. An experimental study in the dog.
- 2005
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Ingår i: Journal of clinical periodontology. - 0303-6979. ; 32:5, s. 435-40
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The current experiments had three aims (i) to determine whether the absence of the periodontal ligament (PDL) may alter features of the healing of an extraction socket, (ii) to examine if there were differences in the proportion of different tissues in resolved extraction sockets and surgically produced defects after 3 months of healing, (iii) to study the influence of different biomaterials on the healing of surgically produced bone defects. MATERIAL AND METHODS: Extraction sites: In five dogs, the 4th mandibular pre-molars were hemi-sected and the distal roots were removed. The extraction socket of one of the pre-molars was instrumented to eliminate all remnants of the PDL tissue. The socket of the contra-lateral pre-molar was left without instrumentation. The dogs were sacrificed after 3 months of healing. Defect sites: In five dogs, the pre-molars and 1st molars on both sides of the mandible were first removed and 3 months of healing allowed. After this interval three standardized cylindrical defects were prepared in each side of the mandible. The defects were 3.5 mm in diameter and 8 mm deep. In each quadrant one defect was grafted with Bio-Oss Collagen, one with Collagen Sponge and one defect was left non-grafted. The dogs were sacrificed 3 months after the grafting procedure. RESULTS: Extraction sites: The two categories of extraction sockets did not differ with respect to gross morphological features. The tissue of the extraction sites, apical of a newly formed bone bridge, was dominated by bone marrow. Few trabeculae of lamellar bone were also present. Defect sites: The non-augmented defect was sealed by a hard-tissue bridge. In the central and apical portions of the defect bone marrow made up about 61%, and mineralized bone 39% of the tissues. The invagination of the surface of this crestal bone was 0.8+/-0.3 mm. The defect augmented with Collagen Sponge was covered by a hard-tissue bridge 38% of the tissue within the defect was made up of bone marrow while the remaining 62% was occupied by mineralized bone. The invagination of the hard-tissue bridge was on the average 0.6+/-0.1 mm. In defects augmented with Bio-Oss Collagen the biomaterial occupied a substantial portion of the tissue volume. Eighty-five percent of the periphery of the Bio-Oss particles were found to be in direct contact with newly formed mineralized bone. Woven bone and bone marrow made up 47% and 26% of the newly formed tissue. The invagination of the most coronal part of the bone defect was 0.1+/-0.1 mm. CONCLUSION: Sockets that following tooth removal had their PDL tissue removed exhibited similar features of healing after 3 months as sockets which had the PDL retained. The tissues present in an extraction site appeared to be more mature than those present in a surgically produced defect of similar dimension. The Bio-Oss Collagen augmented defect exhibited less wound shrinkage than the non-augmented defect.
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| 9. |
- Chinn, Susan, et al.
(författare)
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Bronchial responsiveness in atopic adults increases with exposure to cat allergen
- 2007
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 176:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The association of asthma with sensitization and allergen exposure is known to be complex. There have been few studies of bronchial responsiveness in relation to both risk factors in adults. Objectives: To determine the relation of bronchial responsiveness to allergen exposure and IgE sensitization in a community study taking into account the major determinants of bronchial responsiveness in adulthood. Methods: Cross-sectional data were drawn from 1,884 participants in 20 centers in the European Community Respiratory Health Survey follow-up, which included measurement of house dust mite and cat allergen in mattress dust samples, and IgE sensitization to four allergens. Bronchial responsiveness to methacholine was expressed as a continuous variable, and analyzed by multiple regression. Measurements and Main Results: The trend toward greater bronchial responsiveness with increasing exposure to cat allergen was greater in those sensitized to any of the four allergens than those not sensitized (p = 0.001); there was no significant interaction between cat sensitization and Fel d 1 exposure. No trend was found with house dust mite allergen exposure. The difference in bronchial responsiveness between those exposed to the highest levels compared with the lowest was approximately –2.02 doubling doses of PD20 (95% confidence interval, –3.06 to –0.97), and nearly as great in those exposed to more moderate levels. Conclusions: Cat allergen exposure at moderate levels may be harmful to all atopic adults. The clinical implication is that it is insufficient to test patients with asthma for cat sensitization; all atopic individuals may benefit from reduced cat exposure.
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| 10. |
- Druker, Brian J., et al.
(författare)
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Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
- 2006
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 355:23, s. 2408-2417
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
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