Showing papers by "Robert McKenna published in 2001"
TL;DR: Caution is warranted in the use of lung-volume-reduction surgery in patients with emphysema who have a low FEV1 and either homogeneous emphySEma or a very low carbon monoxide diffusing capacity, and these patients are at high risk for death after surgery and also are unlikely to benefit from the surgery.
Abstract: Background Lung-volume-reduction surgery is a proposed treatment for emphysema, but optimal selection criteria have not been defined. The National Emphysema Treatment Trial is a randomized, multicenter clinical trial comparing lung-volume-reduction surgery with medical treatment. Methods After evaluation and pulmonary rehabilitation, we randomly assigned patients to undergo lung-volume-reduction surgery or receive medical treatment. Outcomes were monitored by an independent data and safety monitoring board. Results A total of 1033 patients had been randomized by June 2001. For 69 patients who had a forced expiratory volume in one second (FEV1) that was no more than 20 percent of their predicted value and either a homogeneous distribution of emphysema on computed tomography or a carbon monoxide diffusing capacity that was no more than 20 percent of their predicted value, the 30-day mortality rate after surgery was 16 percent (95 percent confidence interval, 8.2 to 26.7 percent), as compared with a rate of 0 percent among 70 medically treated patients (P Conclusions Caution is warranted in the use of lung-volume-reduction surgery in patients with emphysema who have a low FEV1 and either homogeneous emphysema or a very low carbon monoxide diffusing capacity. These patients are at high risk for death after surgery and also are unlikely to benefit from the surgery.
558 citations
TL;DR: The first structure of a geminivirus particle is determined, the Nigerian strain of Maize streak virus (MSV-N), using cryo-electron microscopy and three-dimensional image reconstruction methods and the reconstructed density map and pseudo-atomic model demonstrate that the geminate particle has a stable, defined structure.
194 citations
TL;DR: 4-MI appears to compensate for the absence of His 64 and rescues the catalytic activity of the H64A HCA II mutant, which strongly suggests that the out conformation of His64 is effective in the transfer of protons between the zinc-bound solvent molecule and solution.
Abstract: Histidine 64 in human carbonic anhydrase II (HCA II) functions in the catalytic pathway of CO2 hydration as a shuttle to transfer protons between the zinc-bound water and bulk water. Catalysis of the exchange of 18 O between CO2 and water, measured by mass spectrometry, is dependent on this proton transfer and was decreased more than 10-fold for H64A HCA II compared with wild-type HCA II. The loss of catalytic activity of H64A HCA II could be rescued by 4-methylimidazole (4-MI), an exogenous proton donor, in a saturable process with a maximum activity of 40% of wild-type HCA II. The crystal structure of the rescued complex at 1.6 A resolution shows 4-MI bound in the active-site cavity of H64A HCA II, through ﷿ stacking interactions with Trp 5 and H-bonding interactions with water molecules. In this location, 4-MI is about 12 A from the zinc and approximates the observed "out" position of His 64 in the structure of the wild-type enzyme. 4-MI appears to compensate for the absence of His 64 and rescues the catalytic activity of the H64A HCA II mutant. This result strongly suggests that the out conformation of His 64 is effective in the transfer of protons between the zinc-bound solvent molecule and solution.
96 citations
TL;DR: Expiratory airflow improved due to the increase in both lung elastic recoil and small airway intraluminal caliber, and palliative clinical and physiological improvement in 9 of 26 patients at 3 yr, 7 at 4 yr, and 2 at 5 yr.
Abstract: Current datum more than 2 yr after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline and 5-yr results in 26 symptomatic patients (mean age 67 +/- 6 yr) (mean +/- SD) who underwent bilateral, targeted upper lobe stapled LVRS using video-assisted thoracoscopy. Baseline forced expiratory volume in 1 s (FEV(1)) was 0.7 +/- 0.2 L (mean +/- SD), 29 +/- 10% predicted. Following LVRS, with none lost to follow-up, mortality due to respiratory failure at 0.5, 1, 2, 3, 4, and 5 yr was 4%, 4%, 19%, 31%, 46%, and 58%, respectively. Increase above baseline for FEV(1) > 200 ml and/or FVC > 400 ml at 1, 2, 3, 4, and 5 yr post-LVRS was noted in 73%, 46%, 35%, 27%, and 8% of all patients; decrease in dyspnea grade >/= 1 in 88%, 69%, 46%, 27%, and 15%; and elimination of initial oxygen dependence in 18 patients in 78%, 50%, 33%, 22%, and 0%, respectively. Expiratory airflow improved due to the increase in both lung elastic recoil and small airway intraluminal caliber. Five patients decreased FEV(1) 141 +/- 60 ml/yr and FVC 102 +/- 189 ml/yr over 3.8 +/- 1.2 yr post-LVRS, similar to their pre-LVRS rate of decline. In the 11 patients who survived 5 yr, at 0.5-1.0 yr post-LVRS peak increase in FEV(1) was 438 +/- 366 ml, with a decline of 149 +/- 157 ml the following year and 78 +/- 59 ml/yr over 4.0-4.5 yr. Bilateral LVRS provided palliative clinical and physiological improvement in 9 of 26 patients at 3 yr, 7 at 4 yr, and 2 at 5 yr.
94 citations
TL;DR: The observation that antibodies against a single target peptide in the ADV capsid can mediate both neutralization and ADE may explain the failure of capsid-based vaccines.
Abstract: Aleutian mink disease parvovirus (ADV) causes a persistent infection associated with circulating immune complexes, immune complex disease, hypergammaglobulinemia, and high levels of antiviral antibody. Although antibody can neutralize ADV infectivity in Crandell feline kidney cells in vitro, virus is not cleared in vivo, and capsid-based vaccines have proven uniformly ineffective. Antiviral antibody also enables ADV to infect macrophages, the target cells for persistent infection, by Fc-receptor-mediated antibody-dependent enhancement (ADE). The antibodies involved in these unique aspects of ADV pathogenesis may have specific targets on the ADV capsid. Prominent differences exist between the structure of ADV and other, more-typical parvoviruses, which can be accounted for by short peptide sequences in the flexible loop regions of the capsid proteins. In order to determine whether these short sequences are targets for antibodies involved in ADV pathogenesis, we studied heterologous antibodies against several peptides present in the major capsid protein, VP2. Of these antibodies, a polyclonal rabbit antibody to peptide VP2:428-446 was the most interesting. The anti-VP2:428-446 antibody aggregated virus particles into immune complexes, mediated ADE, and neutralized virus infectivity in vitro. Thus, antibody against this short peptide can be implicated in key facets of ADV pathogenesis. Structural modeling suggested that surface-exposed residues of VP2:428-446 are readily accessible for antibody binding. The observation that antibodies against a single target peptide in the ADV capsid can mediate both neutralization and ADE may explain the failure of capsid-based vaccines.
47 citations
TL;DR: LVRS is the first treatment to demonstrate substantial improvement in pulmonary function and quality of life for selected patients with emphysema, and several randomized, prospective studies are now comparing LVRS with maximal medical management.
Abstract: Lung volume reduction surgery (LVRS) is a promising new treatment for selected patients with moderate to severe symptoms of emphysema. Medical management, including pulmonary rehabilitation, has been shown to reduce oxygen requirements during exercise and probably to reduce hospitalization for patients with severe emphysema, but it does not improve pulmonary function. By improving the elastic recoil of the lung, LVRS is the first treatment to demonstrate substantial improvement in pulmonary function and quality of life for selected patients with emphysema. The most important selection factor for LVRS is the presence of a heterogeneous pattern of emphysema. Because it is found in only 20% of patients with emphysema, only a small number of patients are candidates for the procedure. Published reports indicate that the optimal operative technique appears to be a bilateral staple operation during a single anesthetic. This procedure offers a 68% chance of oxygen independence, 85% chance of prednisone independence, and 60% to 70% improvement in pulmonary function for patients with an upper lobe distribution of emphysema. The long-term benefits of the procedure are currently unknown, so several randomized, prospective studies are now comparing LVRS with maximal medical management.
16 citations
TL;DR: In this article, human carbonic anhydrase II with a specific point mutation, His 64 to Ala, have been grown in a solution of ammonium sulfate in the presence of mercury chloride.
Abstract: Crystals of human carbonic anhydrase II with a specific point mutation, His 64 to Ala, have been grown in a solution of ammonium sulfate in the presence of mercury chloride. The crystals appear in approximately two weeks and belong to the monoclinic space group P21, with unit cell parameters of a = 42.2 A, b = 41.4 A, c = 71.9 A , beta= 104.2 o and one carbonic anhydrase molecule in the asymmetric unit. The crystals diffract X-rays beyond 1.0 A resolution. These crystals, soaked with exogenous proton acceptor donors, will be used in X-ray and neutron diffraction studies to map the fine water structure “proton wire” in the active site of carbonic anhydrase and to assign the intra- and intermolecular proton transfer pathway(s) from the zinc-bound water out to the bulk solvent.
3 citations