| 1. |
- Smits, KM, et al.
(författare)
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Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:2, s. 266-270
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20,938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYPIAI, GSTMI, GSTTI, NAT2 and GSTPI. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
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| 2. |
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| 3. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
- 2023
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 8:81, s. eade0958-
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Tidskriftsartikel (refereegranskat)abstract
- Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2′ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
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| 4. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
- 2023
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 8:81, s. eade0958-
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Tidskriftsartikel (refereegranskat)abstract
- Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2′ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
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| 5. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2
- 2022
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the fourgenera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2’ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive withOrthocoronavirinae, including SARS-CoV-2 variants.Broadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery.
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| 6. |
- Dellaca, Raffaele L., et al.
(författare)
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Lung recruitment assessed by total respiratory system input reactance
- 2009
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 35:12, s. 2164-2172
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: ALI and ARDS are associated with lung volume derecruitment, usually counteracted by PEEP and recruitment maneuvers (RM), which should be accurately tailored to the patient's needs. The aim of this study was to investigate the possibility of monitoring the amount of derecruited lung by the forced oscillation technique (FOT). METHODS: We studied six piglets (26 +/- 2.5 kg) ventilated by a mechanical ventilator connected to a FOT device that produced sinusoidal pressure forcing at 5 Hz. The percentage of non-aerated lung tissue (V (tiss)NA%) was measured by whole-body CT scans at end-expiration with zero end-expiratory pressure. Respiratory system oscillatory input reactance (X (rs)) was measured simultaneously to CT and used to derive oscillatory compliance (C (X5)), which we used as an index of recruited lung. Measurements were performed at baseline and after several interventions in the following sequence: mono-lateral reabsorption atelectasis, RM, bi-lateral derecruitment induced by broncho-alveolar lavage and a second RM. RESULTS: By pooling data from all experimental conditions and all pigs, C (X5) was linearly correlated to V (tiss)NA% (r (2) = 0.89) regardless of the procedure used to de-recruit the lung (reabsorption atelectasis or pulmonary lavage). Separate correlation analysis on single pigs showed similar regression equations, with an even higher coefficient of determination (r (2) = 0.91 +/- 0.07). CONCLUSION: These results suggest that FOT and the measurement of C (X5) could be a useful tool for the non-invasive measurement of lung volume recruitment/derecruitment.
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| 7. |
- Dellaca, Raffaele L., et al.
(författare)
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Optimisation of positive end-expiratory pressure by forced oscillation technique in a lavage model of acute lung injury
- 2011
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 37:6, s. 1021-1030
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated whether oscillatory compliance (C-X5) measured by forced oscillation technique (FOT) at 5 Hz may be useful for positive end-expiratory pressure (PEEP) optimisation. We studied seven pigs in which lung injury was induced by broncho-alveolar lavage. The animals were ventilated in volume control mode with a tidal volume of 6 ml/kg. Forced oscillations were superimposed on the ventilation waveform for the assessment of respiratory mechanics. PEEP was increased from 0 to 24 cmH(2)O in steps of 4 cmH(2)O and subsequently decreased from 24 to 0 in steps of 2 cmH(2)O. At each 8-min step, a CT scan was acquired during an end-expiratory hold, and blood gas analysis was performed. C-X5 was monitored continuously, and data relative to the expiratory hold were selected and averaged for comparison with CT and oxygenation. Open lung PEEP (PEEPol) was defined as the level of PEEP corresponding to the maximum value of C-X5 on the decremental limb of the PEEP trial. PEEPol was on average 13.4 (+/- 1.0) cmH(2)O. For higher levels of PEEP, there were no significant changes in the amount of non-aerated tissue (V-tissNA%). In contrast, when PEEP was reduced below PEEPol, V-tissNA% dramatically increased. PEEPol was able to prevent a 5% drop in V-tissNA% with 100% sensitivity and 92% specificity. At PEEPol V-tissNA% was significantly lower than at the corresponding PEEP level on the incremental limb. The assessment of C-X5 allowed the definition of PEEPol to be in agreement with CT data. Thus, FOT measurements of C-X5 may provide a non-invasive bedside tool for PEEP titration.
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| 8. |
- Kostic, Peter, et al.
(författare)
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Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury : a controlled experimental study in pigs with saline lavage lung injury
- 2011
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 15:3, s. R126-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Protocols using high levels of positive end-expiratory pressure (PEEP) in combination with low tidal volumes have been shown to reduce mortality in patients with severe acute respiratory distress syndrome (ARDS). However, the optimal method for setting PEEP is yet to be defined. It has been shown that respiratory system reactance (Xrs), measured by the forced oscillation technique (FOT) at 5 Hz, may be used to identify the minimal PEEP level required to maintain lung recruitment. The aim of the present study was to evaluate if using Xrs for setting PEEP would improve lung mechanics and reduce lung injury compared to an oxygenation-based approach. Methods: 17 pigs, in which acute lung injury (ALI) was induced by saline lavage, were studied. Animals were randomized into two groups: in the first PEEP was titrated according to Xrs (FOT group), in the control group PEEP was set according to the ARDSNet protocol (ARDSNet group). The duration of the trial was 12 hours. In both groups recruitment maneuvers (RM) were performed every 2 hours, increasing PEEP to 20 cmH(2)O. In the FOT group PEEP was titrated by monitoring Xrs while PEEP was reduced from 20 cmH(2)O in steps of 2 cmH(2)O. PEEP was considered optimal at the step before which Xrs started to decrease. Ventilatory parameters, lung mechanics, blood gases and hemodynamic parameters were recorded hourly. Lung injury was evaluated by histopathological analysis. Results: The PEEP levels set in the FOT group were significantly higher compared to those set in the ARDSNet group during the whole trial. These higher values of PEEP resulted in improved lung mechanics, reduced driving pressure, improved oxygenation, with a trend for higher PaCO(2) and lower systemic and pulmonary pressure. After 12 hours of ventilation, histopathological analysis showed a significantly lower score of lung injury in the FOT group compared to the ARDSNet group. Conclusions: In a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.
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