Joseph Taylor

Iron phosphine complexes prove to be good precatalysts for the cross-coupling of alkyl, benzyl, and allyl halides with not only aryl triorganoborate salts but also related aluminum-, gallium-, indium-, and thallium-based nucleophiles. Mechanistic studies revealed that while Fe(I) can be accessed on catalytically relevant time scales, lower average oxidation states are not formed fast enough to be relevant to catalysis. EPR spectroscopic studies reveal the presence of bis(diphosphine)iron(I) complexes in representative catalytic reactions and related processes with a range of group 13 nucleophiles. Isolated examples were studied by Mössbauer spectroscopy and single-crystal X-ray structural analysis, while the electronic structure was probed by dispersion-corrected B3LYP DFT calculations. An EPR study on an iron system with a bulky diphosphine ligand revealed the presence of an S = 1/2 species consistent with the formation of a mono(diphosphine)iron(I) species with inequivalent phosphine donor environments. DFT analysis of model complexes allowed us to rule out a T-shaped Fe(I) structure, as this is predicted to be high spin.

<h3>Background</h3> Patients with head and neck cancer often experience debilitating speech, eating, and respiratory problems as well as the psychological effects of loss of function and change in body image. These patients often become unemployed as a result of their disease process, which adds financial burden to their already stressful lives. Yet the specific factors associated with unemployment have not been systematically studied. <h3>Methods</h3> This multisite study used survey and chart data to determine the predictors of work-related disability. <h3>Results</h3> Of the 384 patients who were working prior to their diagnosis of head and neck cancer, 52% (n = 201) were disabled by their cancer treatment. Multivariate analysis demonstrated significant links between disability and chemotherapy (odds ratio [OR], 3.4;<i>P</i>&lt;.001), neck dissection status (OR, 2.3;<i>P</i>= .01), pain scores (OR, 1.2;<i>P</i>= .01), and time since diagnosis (OR, 0.9;<i>P</i>= .04). <h3>Conclusions</h3> More than half of the patients in this study were disabled by their head and neck cancer or treatment. Patients with head and neck cancer who have undergone chemotherapy or neck dissection or have high pain scores are at increased risk for disability from their cancer or their treatment. Efforts to prevent (if possible), better assess, and treat pain and other adverse effects of head and neck cancer treatments may also have the potential to reduce patient disability.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLimited degradation of the third component (C3) of human complement by human leukocyte elastase (HLE): partial characterization of C3 fragmentsJ. C. Taylor, I. P. Crawford, and T. E. HugliCite this: Biochemistry 1977, 16, 15, 3390–3396Publication Date (Print):July 26, 1977Publication History Published online1 May 2002Published inissue 26 July 1977https://doi.org/10.1021/bi00634a016RIGHTS & PERMISSIONSArticle Views106Altmetric-Citations72LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

Abstract Affinity chromatography permits the purification of 1–3 mg of human leukocyte elastase from the leukocytes contained in 500 ml of whole blood. Lysosomal granule proteins are extracted from polymorphonuclear leukocytes and subjected to chromatography on a column of elastin-Sepharose. Contaminating proteins are eluted with buffer containing 1 m NaCl and then elastase activity is eluted with buffer containing 8 m urea. The enzyme retains all of its esterase activity against N -t-BOC- l -alanine p -nitrophenyl ester after exposure to 8 m urea and retains 22% of its activity in the presence of 1% sodium dodecyl sulfate. In sodium dodecyl sulfate and 2-mercaptoethanol leukocyte elastase undergoes autolysis giving rise to several low molecular weight fragments. The molecular weight of the native enzyme is found to be 22.000 by both gel filtration and sodium dodecyl sulfate—acrylamide gel electrophoresis. A characteristic set of four isozymes is seen after acrylamide disc gel electrophoresis at pH 4.5. All bands are active against elastin and also contain carbohydrate by the periodic acid-Schiff stain. On the basis of stain intensity, the slower moving isozymes appear to be richest in carbohydrate. Active leukocyte elastase forms a complex with α 1 -antitrypsin in a 1:1 molar ratio. The elastase must be enzymatically active for complex formation to occur.

The Tamm-Dancoff equations are expressed in a concise four-dimensional form. The difficulty of renormalizing the new Tamm-Dancoff equation of Dyson is discussed. The L\'evy-Klein approximation to the Bethe-Salpeter equation is derived as an approximation to the old Tamm-Dancoff equation, and a new renormalizable equation is derived analogously as an approximation to the new Tamm-Dancoff equation. The latter approximation is better than the former.

Introduction: Skeletal reconstruction in severe grades of hemifacial microsomia (HFM) continues to be challenging. Traditional techniques of autografts and osseous distraction for reconstruction of the glenoid fossa, condyle, and ramus can fall short of expectations and can create new problems. This intercontinental study analyzes the role of alloplastic skeletal rehabilitation in severe HFM. Methods: Ten consecutive patients with Pruzansky grade III HFM were reconstructed between October 2014 and July 2017 at 2 craniofacial centers following the same protocol. Data were gathered retrospectively from the medical records, including photographs and virtual planning records. Pre and postoperative photos were taken to compare occlusal status, interincisal opening, sagittal mandibular projection, and posterior facial height. Alloplastic reconstruction was accomplished using a custom designed titanium implant. Results: Ten consecutive skeletally mature patients with HFM with failed traditional reconstructions were successfully treated with virtually planned alloplastic reconstructions (11 joints) and simultaneous orthognathic surgery. The glenoid fossa, condyle, and ramus on the affected sides were reconstructed with custom designed titanium implants. All patients achieved occlusal stabilization, normalization of posterior facial height and sagittal mandibular projection, and maintenance or improved inter-incisal opening. There were no major complications or repeated surgeries. Follow-up ranges from 6 to 50 months. Conclusion: Alloplastic reconstruction allows for precise vertical reconstruction of the ramus and condyle and sagittal repositioning of the mandibular body. The glenoid fossa component is firmly anchored to the skull base assuring a stable centric relation on the reconstructed side. Consistent and acceptable results can be achieved in skeletally mature patients.

Evaluate the utility and explore the cost-effectiveness of mandatory gross or pathologic analysis of routine tonsillectomy specimens in children.Case series with chart review.Tertiary care children's hospital.Retrospective case series of results of pathologic analysis of tonsillectomy specimens from all pediatric patients who underwent tonsillectomy between 1996 and 2008 (n = 5235). The results of pathologic evaluation of routine and nonroutine specimens were evaluated, and an economic analysis of alternative methods of specimen handling was performed.Zero cases of unsuspected pathology were identified on planned gross specimen evaluation (n = 4186), resulting in an estimated prevalence of 0 to 0.00088 (95% confidence interval [CI]). Positive pathologic findings on microscopic analysis (n = 1066) were only identified in posttransplant patients (10/63; 95% CI, 0.079-0.27) and cases of surgeon suspicion (8/78; 0.045-0.19). No cases were identified among the 17 undergoing microscopic pathologic analysis on the basis of pathologist suspicion on gross evaluation (95% CI, 0-0.20). From an economic standpoint, microscopic evaluation of routine pediatric tonsillectomy specimens appears to be superior to gross evaluation but with an estimated cost of $766,500 per case of unsuspected lymphoma identified.This study identifies a very low prevalence of unsuspected pathology on gross pathologic analysis of routine tonsillectomy specimens in children. Exploration of the cost implications suggests that such a practice is not a cost-effective use of limited health care resources. Microscopic examination is appropriate for posttransplantation patients and in cases of surgeon suspicion.

Geometric fluctuations of the density mode in a fractional quantum Hall (FQH) state can give rise to a nematic FQH phase, a topological state with a spontaneously broken rotational symmetry. While experiments on FQH states in the second Landau level have reported signatures of putative FQH nematics in anisotropic transport, a realistic model for this state has been lacking. We show that the standard model of particles in the lowest Landau level interacting via the Coulomb potential realizes the FQH nematic transition, which is reached by a progressive reduction of the strength of the shortest-range Haldane pseudopotential. Using exact diagonalization and variational wave functions, we demonstrate that the FQH nematic transition occurs when the system's neutral gap closes in the long-wavelength limit while the charge gap remains open. We confirm the symmetry-breaking nature of the transition by demonstrating the existence of a ``circular moat'' potential in the manifold of states with broken rotational symmetry, while its geometric character is revealed through the strong fluctuations of the nematic susceptibility and Hall viscosity.

In 2013, Becky Lynch, an Irish professional wrestler, was signed by WWE, marking the beginning of her rise to superstardom. By 2020, Lynch had become a major WWE star, participating in the first women's Wrestlemania main event with Charlotte Flair and Ronda Rousey. While not the first Irish wrestler in WWE, Lynch is the first to reach superstar status. This article focuses on her portrayal in Irish media, which often finds itself in a unique position between sport and entertainment. Despite her popularity, professional wrestling's blend of sport and entertainment leads to its coverage primarily in entertainment sections, occasionally crossing into sports biographies. Through an analysis of Lynch's media portrayal from 2013 to her 2020 maternity leave, this piece explores the tension between her self-presentation and media representation, arguing that the wrestling's ambiguous status and traditional gender biases in sports reporting downplay Lynch's athletic achievements by emphasizing her femininity.

<h3>Background</h3> Aprepitant, a substance P neurokinin-1 (NK1) receptor antagonist, is licensed for the prevention of acute and delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy. Case: A 33 year-old male with metastatic gastro-oesophageal cancer had multiple admissions for refractory nausea and vomiting following insertion of an oesophageal stent. He was unable to sufficiently tolerate an oral diet and required IV hydration. Systemic cancer treatment was suspended pending resolution. The patient had multiple lengthy hospital admissions over a period of months with refractory symptoms. Action: Mechanical issues with the stent, stent removal and central causes were excluded. Multiple anti-emetic agents were trialled in combination and with varying routes of administration without significant symptomatic improvement. A trial of aprepitant was proposed as an off-licence therapy. Outcome: 165 milligrams of aprepitant was given orally every 3 days and then up titrated to once daily with significant symptomatic improvement enabling the patient to tolerate an oral diet. The patient remained stable at 12 weeks and has been accepted into 2 clinical trials for potential further cancer treatment. What now? Further research of NK1 inhibitors for indications other than chemotherapy-induced nausea and vomiting is indicated. Learning Points: 1) Although NK1 inhibitors are only licenced and funded for prevention of chemotherapy-induced nausea and vomiting we have demonstrated their utility in refractory nausea and vomiting not related to chemotherapy and their use over a much longer time-period. 2) Prolonged nausea and vomiting are not frequently reported complications of oesophageal stent insertion but patients should be counselled on these rare but serious complications prior to insertion. 3) The use of aprepitant in this case has allowed a patient deemed unsuitable for further life prolonging anti-cancer therapy despite multiple anti-emetics, including subcutaneous levomepromazine, to become eligible and have significantly improved quality of life.

We showed that tumor cells with wild-type p53 and high levels of Bcl-x(L) are cisplatin resistant but are induced to undergo apoptosis by (-)-gossypol, making this a promising agent for overcoming cisplatin resistance. However, some cells in a population with this phenotype are not killed and continue to survive. Conversely, tumor cells with low Bcl-x(L) expression and either wild type or mutant p53 are relatively cisplatin sensitive and do not exhibit such high levels of apoptosis. However, these do undergo progressive loss of viability after (-)-gossypol that may not be tumor specific. We sought to elucidate the basis for these observations using cDNA microarray analysis of (-)-gossypol treated cisplatin sensitive and resistant cells. Genes in the reactive oxygen species (ROS) pathway were highly upregulated in response to (-)-gossypol. The upregulation was of much greater magnitude in cisplatin sensitive than resistant cells. Staining with an oxidation reporter dye confirmed differential induction of ROS in tumor cells with low Bcl-x(L). As (-)-gossypol is known to undergo oxidative metabolism in vivo, ROS generation may be responsible for both off-target cytotoxicity and inactivation of the drug. In agreement with this hypothesis, oxidation of (-)-gossypol by pre-treatment with hydrogen peroxide eliminated its activity. Combined treatment with the antioxidant N-acetyl-cysteine (NAC) to block ROS increased (-)-gossypol-induced cytotoxicity to tumor but not normal cells. Furthermore, NAC increased the induction of apoptosis as measured by the sub-G(1) population, in both cisplatin sensitive and resistant cells. We postulate that concurrent treatment with antioxidant to block ROS prevents oxidative inactivation of (-)-gossypol and limits off-target toxicity allowing more potent (-)-gossypol-induced anti-tumor activity.

To determine the effectiveness of cricotracheal resection and hilar release for high-grade, long-segment airway stenosis.We identified 16 patients who underwent cricotracheal resection and hilar release, performed from January 1, 2004, through December 31, 2008, and conducted a retrospective review, emphasizing preoperative findings, operative technique, postoperative course, and results. Complete data sets were available for all patients.Tertiary care children's hospital.The study population comprised 16 patients younger than 18 years who underwent cricotracheal resection and hilar release performed by a thoracic airway team. All patients had high-grade, long-segment subglottic stenosis or severe, long-segment tracheomalacia.Cricotracheal resection with hilar release.Decannulation rate and dehiscence rate.Of the 16 patients, 15 were successfully decannulated. The one patient who was not decannulated remained ventilator dependent and has regained speech. There were no incidents of anastomotic dehiscence.Cricotracheal resection with hilar release is a novel and effective way to approach the problem of severe airway stenosis.

This report describes an assay with the capability of detecting antioxidant activity of plasma and of purified proteins. The method is based on the enzymatic oxidation of plasma elastase inhibitory capacity of enzyme(s) in extracts of human lysosomes in the presence of hydrogen peroxide, chloride, and magnesium ions. Using this method we measured the antioxidant activity of the plasma of 59 subjects. We detected a strong relationship between a deficiency in the antioxidant activity of plasma and the presence of a family history of lung disease (p less than 0.005), and an abnormal mean FEV1/FVC ratio (p less than 0.005).

When leukocyte lysosomal extracts are used as a source of elastase and are combined with a fraction of plasma containing sufficient alpha 1-protease inhibitor (alpha 1-Pi) to inhibit all but 30 to 40% of the elastase amidase activity, elastolysis occurs at 69% of the rate of the uninhibited elastase controls (0.125 M NaCl; pH, 6.5). Proteolysis of elastin requires the presence of NaCl. At pH 8.6, elastolysis is decreased to 30 to 40% of free elastase controls by 1.0 M NaCl. At pH 6.5, on the other hand, elastolysis is increased to 83% of the control values by these higher NaCl concentrations. The activity of human leukocyte myeloperoxidase is optimal at pH 6 to 6.5 and at NaCl concentrations between 0.25 and 1.0 M. Purified myeloperoxidase, alpha 1-Pi, and elastase, in the presence of NaCl and hydrogen peroxide, can reproduce this phenomenon at pH 6.5, suggesting that the occurrence of elastolysis in lysosomal extract-plasma mixtures may in part be a result of the oxidative inactivation of alpha 1-Pi by myeloperoxidase present in the lysosomal extract. Human ceruloplasmin, the major antioxidant of plasma, inhibits this myeloperoxidase-dependent reaction, without interfering either with free elastase activity or with the appearance of activity in plasma-lysosomal extract mixtures at pH 8.6. The "antioxidant" activity of ceruloplasmin is inhibited by azide. These results suggest that antioxidants such as ceruloplasmin may be an important determinant of lung defense in persons chronically exposed to oxidants.

In 9 alpha1-antitrypsin-deficient (PiZZ) persons 40 to 53 years of age, the relationships between the concentration of elastolytic protease of polymorphonuclear leukocyte granules and cigarette smoking, and the degree of abnormality in detailed pulmonary function tests were explored. Regardless of the statistical analytic approach used, elastase concentration was related more frequently and significantly than smoking history to the degree of abnormality observed in tests of pulmonary function. The data suggest that the severity of pulmonary dysfunction in PiZZ persons may be determined by variables other than age and cigarette smoking, including the concentration of elastolytic protease in leukocyte lysosomes.

This case report describes a successful management of cardiac arrest in a patient in prone position during posterior craniotomy. Commencement of CPR in the prone position minimised the no flow time and avoided the risks of turning a patient with an open cranium. No obvious surgical insult such as haemorrhage, air embolus or dural traction preceded the arrest. The patient had a structurally abnormal heart, which may have predisposed him to arrhythmia. Defibrillation in the prone position was successful. Prone resuscitation should always be considered as a first response in the event of cardiac arrest during prone surgery.

Results from the completed Phase 1 Upgrade of the Compact Muon Solenoid (CMS) Level-1 Calorimeter Trigger are presented. The upgrade was performed in two stages, with the first running in 2015 for proton and heavy ion collisions and the final stage for 2016 data taking. The Level-1 trigger has been fully commissioned and has been used by CMS to collect over 43 fb−1 of data since the start of the Run II of the Large Hadron Collider (LHC). The new trigger has been designed to improve the performance at high luminosity and large number of simultaneous inelastic collisions per crossing (pile-up). For this purpose it uses a novel design, the Time Multiplexed Trigger (TMT), which enables the data from an event to be processed by a single trigger processor at full granularity over several bunch crossings. The TMT design is a modular design based on the μTCA standard. The trigger processors are instrumented with Xilinx Virtex-7 690 FPGAs and 10 Gbps optical links. The TMT architecture is flexible and the number of trigger processors can be expanded according to the physics needs of CMS. Sophisticated and innovative algorithms are now the core of the first decision layer of the experiment. The system has been able to adapt to the outstanding performance of the LHC, which ran with an instantaneous luminosity well above design. The performance of the system for single physics objects are presented along with the optimizations foreseen to maintain the thresholds for the harsher conditions expected during the LHC Run II and Run III periods.

Knowledge of tumor antigenic expression is crucial to the design of therapeutic strategy. A murine monoclonal antibody (BE4) against a human melanoma membrane antigen, was used to study the in vitro expression of this antigen. By membrane immunofluorescence, BE4 reacted against 5 of 8 melanoma lines as compared to zero of 13 other cell populations. Using flow cytometry, the antigenic M14 CEM melanoma cells consisted of 40% to 60% of the total cell population. Dual-parameter measurements of DNA content and membrane antigen demonstrated that the nonantigenic cells were predominantly in G0/G1 phase, whereas the antigenic cells were distributed throughout the cell cycle. Within one passage, the sorted and recultured nonantigenic population demonstrated a similar proportion of antigenic cells as the unsorted original population. It was concluded that the expression of human melanoma antigen was cell-cycle-dependent. Understanding factors that turn off the expression of antigen in G0/G1 phase may lead to better immunotherapeutic strategies.

This note is about the construction of energy-independent potentials from the Tamm-Dancoff equations, by a systematic method of Klein's. It is shown that, when the method is applied to the new Tamm-Dancoff equation of Dyson, the difficulty of the spurious singularities can be overcome. It is proved further that the old and new Tamm-Dancoff methods give the same potential in the adiabatic limit.

We report what we believe to be the first case of metastatic prostate cancer presenting as sclerosing cholangitis. In a 71-year-old man with known prostate cancer and cholestatic jaundice, an endoscopic retrograde cholangiopancreatography revealed multifocal strictures of both the intrahepatic and extrahepatic biliary system consistent with sclerosing cholangitis. Review of a liver biopsy and cholecystectomy specimen showed metastases from prostate cancer, which stained positively with prostate-specific antigen. Multiple hepatic metastases from prostate cancer should be included among the conditions that simulate primary sclerosing cholangitis on cholangiography.

ABSTRACT The interaction of conduction electrons with a vibrating metallic lattice has been considered by Ziman in terms of non-adiabatic perturbations to the adiabatic approximation of the Born-Oppenheimer theory. This programme is continued to calculate the self-energy of the electrons. When account is taken of the dependence of the energy levels of the adiabatic Hamiltonian itself upon the electron configuration, the final result is the same as the standard one.

A technique is described which allows isoelectric focusing of human granulocyte elastase in thin-layer polyacrylamide gels, with retention of between 70 and 90% of the elastolytic activity. Digestion of elastin was observed to occur between pH 8.13 and 8.3 as well as between pH 8.77 and 9.15. Detection of elastolytic activity and visualization of protein bands following staining of the gels, has been successfully attempted with as little as 20 μg of lysosomal extract (about 2 to 3 μg of elastase).

The granulocyte lysosomal elastase of 17 patients with chronic obstructive pulmonary disease and of 27 normal subjects was examined. Serum a1-antitrypsin phenotypes were identical in the 2 groups: 88 per cent were type PiM and 12 per cent were type PiMS. Electrophoresis of granulocyte lysosomal extracts at pH 8.6 revealed interindividual differences in the electrophoretic mobility of the elastase enzyme. The elastases clustered into 3 regions of electrophoretic mobility, which we designated as fast (>29 mm), intermediate (24 through 29 mm), and slow (<24 mm) migration. A comparison of the number of patients and normal subjects in each electrophoretic category showed an almost 4-fold increase in the prevalence of the slow electrophoretic type of elastase in the patient group compared to the normal subjects. Esterase activity in lysosomal extracts against the synthetic elastase substrate N-t-BOC-L-alanine-p-nitrophenyl ester (NBA) varied within a 4 to 5-fold range in both patient and normal populations. No significant differences in the mean esterase activities between the patient group and the normal group could be detected within each elastase category (slow, intermediate, or fast mobility). The mean elastase NBA esterase activity was lowest in the slow elastase electrophoretic category and highest in the fast elastase type. Mean esterase activity in the intermediate electrophoretic category was intermediate between those of the slow and the fast electrophoretic types of elastase. The increase in the number of patients in the slow electrophoretic category with lowest mean elastase esterase activity suggests that qualitative rather than quantitative aspects of elastase may be critical in the pathogenesis of chronic obstructive pulmonary disease in patients with normal a1-antitrypsin phenotypes.

The interaction of serum alpha 1-antitrypsin with leukocyte elastolytic activity was examined in 71 patients with chronic obstructive pulmonary disease and 46 normal subjects. Residual elastolytic activity was present despite adequate amounts of alpha1-antitrypsin in 33 of the 71 patients compared to 6 of the 46 normal control subjects (P less than 0.001). This elastolytic activity was completely abolished by a specific human leukocyte elastase inhibitor. A crossover study designed to detect the source of this abnormal activity revealed that the plasma fraction containing alpha 1-antitrypsin was responsible for inadequate inhibition in 30 of the 39 cases. The residual elastolytic activity from a given patient did not correlate with the serum alpha 1-antitrypsin concentration, alpha 1-antitrypsin phenotype, or history of smoking. Our data suggest that the abnormal interaction of alhpa 1-antitrypsin with leukocyte elastolytic activity is an important additional variable in the gensis of chronic obstructive pulmonary disease.

A sum rule derived from the covariance of a charge-current commutation relation is contradicted by ϱ-meson dominance.

The Compact Muon Solenoid (CMS) employs a sophisticated two-level online triggering system that has a rejection factor of up to 105. Since the beginning of Run II of LHC, the conditions that CMS operates in have become increasingly challenging. The centre-of-mass energy is now 13 TeV and the instantaneous luminosity currently peaks at 1.5 ×1034 cm−2s−1. In order to keep low physics thresholds and to trigger efficiently in such conditions, the CMS trigger system has been upgraded. A new trigger architecture, the Time Multiplexed Trigger (TMT) has been introduced which allows the full granularity of the calorimeters to be exploited at the first level of the online trigger. The new trigger has also benefited immensely from technological improvements in hardware. Sophisticated algorithms, developed to fully exploit the advantages provided by the new hardware architecture, have been implemented. The new trigger system started taking physics data in 2016 following a commissioning period in 2015, and since then has performed extremely well. The hardware and firmware developments, electron and photon algorithms together with their performance in challenging 2016 conditions is presented.

Describes over seventy trees, cereal grains, vegetables, herbs and spices, with numerous illustrations, and the relevant biblical quote/s.

Fat embolism syndrome (FES) is a severe but underdiagnosed complication of sickle cell disease (SCD) associated with very high mortality and morbidity. It is the result of extensive bone marrow necrosis that leads to release of large amounts of fat droplets in the systemic circulation. FES predominantly affects non-homozygous patients and those with a previously mild course of their illness. It is characterised by severe respiratory failure, neurological involvement, thrombocytopenia and extremely elevated levels of serum ferritin and lactiate dehydrogenase (LDH). Without intervention mortality exceeds 90% while immediate red cell exchange (RCE) substantially increases survival and it is currently the treatment of choice.1 Release of fat droplets in the circulation cause mechanical obstruction of the microvasculature. More than that, circulating phospholipids under the action of secretory phospholipase A2 (sPLA2) are metabolised to arachidonic acid which in turn acts as a substrate for the generation of a plethora of pro-inflammatory cytokines.2 Such mediators have a known nociceptive effect, enhance HbS polymerisation and further red cell sickling but also have the potential of causing direct tissue toxicity leading to end-organ damage.3, 4 Specifically in the brain, cytokines such as TNFα, IL-1, and IL-6 can initiate a positive feedback loop resulting in accumulation of extracellular glutamate which in turn causes great influx of water and intracellular oedema referred to as cytotoxic oedema. The corpus callosum and splenium are particularly susceptible to this effect due to a much higher concentration of cytokine receptors. Cytotoxic lesions of the corpus callosum (CLOCC) have been described in a plethora of conditions causing increased cytokine release such as drug reactions, infections and metabolic disorders5 while involvement of the splenium is invariably present in patients with cerebral FES.1 In addition to pro-inflammatory cytokines, SCD plasma contains several other harmful substances including adhesion molecules, free haemoglobin leading to nitric oxide depletion, arginase and procoagulant factors,6 while substances such as haptoglobin and hemopexin are depleted.7 Despite the increasing use of RCE in recent years, mortality from FES remains substantial while a large number of survivors are left with severe neurocognitive impairment (SNI).8 With that in mind, we have previously advocated addition of therapeutic plasma exchange (TPE) to RCE in order to address the inflammatory environment and potentially improve outcomes.8, 9 Here, we compare outcomes from FES using standard treatment with RCE and combination of RCE and TPE. From an ongoing systematic review of all FES cases ever published, we only selected cases published since 2012 to account for the advances in supportive care and only those where RCE was employed, and outcomes were compared to cases where a combination of RCE and TPE was used. We identified 39 cases treated with RCE alone since 2012. Mortality was 21%, 33% of patients were left with SNI and 13% mild neurological impairment (MNI) while only 33% made a complete recovery (CR). We are aware of 12 cases, published9-12 or in press, (separate from the previous 39), treated with RCE followed by TPE worldwide (eight UK, two Canada, one USA, one Denmark). Nine patients were adults and three patients were children. Six patients had homozygous Hb SS disease, five Hb SC and one Hb Sβ+. All patients, irrespective of genotype, previously had a mild course of their illness. All patients were treated in the intensive care unit and all received adequate and timely RCE to HbS/Hb S + C of 30% or less before plasma exchange. The number of TPE procedures performed varied greatly between cases (1–10) mostly depending on clinical response. There was one death (8%), two patients (17%) suffered MNI while eight patients (75%) achieved CR. It should be noted that there were no survivors left with SNI while the two patients reported as suffering MNI are patients who developed the complication recently, have fully recovered cognitive function but are still in rehabilitation improving from generalised weakness resulting from prolonged hospitalisation and are very likely to achieve CR eventually (Figure 1). Among the patients achieving CR there were patients with extensive brain involvement or respiratory failure requiring mechanical ventilation or even extracorporeal membrane oxygenation. There were no episodes of recurrence of FES among the patients treated with RCE and TPE with a mean follow-up of 26 months (4–108). Three patients had a CLOCC on brain magnetic resonance imaging of whom one was treated with RCE only and two with RCE + TPE. The fact that CLOCCs reflect direct cytokine-induced neurocytotoxicity lends further support to addressing the pro-inflammatory environment. The patient receiving RCE alone survived, but with very SNI, was wheelchair bound, and requiring 24-hr care in an appropriate facility. In contrast, both patients receiving the combination of red cell and plasma exchange had a very good clinical outcome with one achieving CR before discharge from hospital and the other currently recovering speedily with physiotherapy at home (Figure 2). In all cases, TPE was well tolerated with no associated adverse events. These early data suggest a clear benefit from this approach. Even though TPE can sometimes be associated with adverse events,13 it is overall a widely used intervention with a relatively safe profile. Therefore, we recommend its addition to RCE as standard management for FES in SCD. The duration of TPE should be tailored to clinical response as well as the trend in haematological and biochemical markers such as haemoglobin, platelets, serum ferritin and LDH. In these early cases we observed recovery of some very severely affected patients, therefore we recommend persevering with treatment even when signs of response are not immediately evident. Dimitris A. Tsitsikas designed the project and wrote the paper, Susan Rowe, Alessandra Bosch, Caitlyn Hui, Nandini Sadasivam, Nicolaos J. Palaskas, Shivan Pancham, Syed Rizvi, Joseph Taylor, Paul Greaves, Andreas Glenthøj, Marianne Hoffmann and Emma Drasar provided and analysed data and critically reviewed the manuscript and Perla Eleftheriou co-designed the project and critically reviewed the manuscript.

Anorexia nervosa (AN) is a life-threatening disease characterized by significantly low body weight in combination with avoidance of weight gain. In this study, we used the human connectome to test whether brain lesions associated with AN map to a common brain network

A variant of human alpha 1-antitrypsin (alpha 1 AT) was found by acid starch gel electrophoresis and by thin-layer electrofocusing. The variant has an anodal migration velocity almost identical to PiB. It is designated as Pi B Alhambra. Pi B Alhambra was purified to homogeneity from a heterozygous PiM1/PiB Alhambra subject. Specific trypsin inhibitory activity and composition of amino acids and carbohydrates were similar to those of normal PiM1. The structural difference between the normal and the variant inhibitors was elucidated by peptide mapping of their tryptic digests. Two amino acid substitutions, Lys to Asp and Glu to Asp, were found. The amino acid substitution, Gly to Asp, has been found in a common PiM2 variant [1]. The Pi B Alhambra variant presumably originated by two steps of mutation: generation of PiM2 from wild type PiM1 by the substitution Gly to Asp, and subsequent generation of Pi B Alhambra from PiM2 by another substitution, Lys to Asp.

Writing the North of England in the Middle Ages offers a literary history of the North-South divide, examining the complexities of the relationship – imaginative, material, and political – between North and South in a wide range of texts. Through sustained analysis of the North-South divide as it emerges in the literature of medieval England, this study illustrates the convoluted dynamic of desire and derision of the North by the rest of country. Joseph Taylor dissects England's problematic sense of nationhood as one which must be negotiated and renegotiated from within, rather than beyond, national borders. Providing fresh readings of texts such as Chaucer's Canterbury Tales, the fifteenth-century Robin Hood ballads and the Towneley plays, this book argues for the North's vital contribution to processes of imagining nation in the Middle Ages and shows that that regionalism is both contained within and constitutive of its apparent opposite, nationalism.

Early nineteenth-century farmers often sowed their crops on an arbitrarily chosen day every year. Impatient with this practice, naturalist Joseph Taylor (c.1761–1844) presents an alternative method in this work, which first appeared in 1812. He argues that by studying the atmosphere, the behaviour of animals and the condition of local flora, a farmer can not only determine the optimal time for sowing, but also forecast the weather. Including the Shepherd of Banbury's famous rules for judging changes in the weather, alongside remarks on the quality of this wisdom, Taylor's book also draws on a wealth of wider countryside knowledge. He observes, for example, that the flowering of primroses and lettuce occurs at such precise times as to be useful for botanical clocks, while the proximity of bees to their hives and the agitation of dogs suggest oncoming weather conditions.

3202 p53 is a transcription factor known to be implicated in more than half of all humancancers. p53 induces G1 cell cycle arrest and/or apoptosis. Murine double-minute protein (mdm2) is one of the most critical regulators of p53. mdm2 directly binds to p53and blocks its transcriptional activity as wellas acts as an E3 ubiquitin ligase promoting proteasomal degradation. As mdm2 inhibition could increase the magnitude of wild type p53 activation following DNA damage, the use of mdm2 antagonists could be a promising strategy for anti-cancer drug design. Resistance to chemotherapy is a problem encountered in the treatment of head and neck squamous cell carcinoma (HNSCC). We found previously that overexpression of Bcl-xL in combination with wild type p53 in HNSCC cell lines is associated with resistance to cisplatin. The purpose of this study was to look at the effectiveness of a recently developed non-peptide small molecule inhibitor of mdm2 along with cisplatin to see if these agents could be combined for more effective treatment of HNSCC tumors. To study this, we used two HNSCC cell lines: a parental, cisplatin sensitive cell line UM-SCC-74B (low Bcl-xL) and a stably transfected cisplatin resistant cell line UM-SCC-74BxL (very high Bcl-xL). Both cell lines have wild-type p53. Cell lines were treated with cisplatin alone, mdm2 inhibitor alone (MI-63), inactive control alone (MI-61), or in combination (sequentially). For combination treatments, cells were treated with cisplatin first for 4 hours, washed and 24 hours later treated with MI-63 or MI-61. The inhibition of cell growth following treatment was assessed by MTT assay. In the cisplatin sensitive UM-SCC-74B cell line, 49%, 50%, 26% viable cells as compared to control were seen in the cisplatin alone, mdm2 inhibitor alone or the combination treatment arm respectively. Similarly and more importantly, in the cisplatin resistant cell line UM-SCC-74BxL, the combination of cisplatin and mdm2 inhibitor was most effective in inhibiting cell growth (27% viable cells) as compared to treatment with cisplatin alone (70%) or mdm-2 inhibitor alone (50%). The inactive control, MI-61, had no effect on the growth of cells as compared to untreated cells. Similar results were obtained using the clonogenic survival assay. Significantly fewer clones were observed in the combination group in both cell lines as compared to the individual drug treated groups. Cell cycle analysis by propidium iodine staining showed that treating with mdm2 inhibitor alone caused cells to undergo G1 arrest. Cells seemed to arrested at G2/M in the combination treatment group, and this G2/M arrest was higher than the G2/M arrest observed in the cisplatin treated group alone. These results indicate that this mdm2 inhibitor in combination with cisplatin might have a great therapeutic potential in the treatment of chemotherapy resistant tumors with wild type p53.

Ceruloplasmin (Cp) protects α1 protease inhibitor from oxidative inactivation. An abnormality of Cp oxidative inhibition could be involved in the pathogenesis of COPD. Accordingly, we studied the closely interrelated reactions of protease-antiprotease/oxidant-antioxidant. The studies were performed at low pH (5.0) simulating tissue conditions during inflammation. Cp function was expressed as p-phenylene diamine oxidase activity/mg Cp (radial immunodifiusion). Elastase inhibitory activity (EIA) was expressed as the percent decrease of the elastase inhibitor of plasma in the presence of Sepharose-bound elastase. These measurements were made in plasma randomly selected from a collection of specimens from healthy subjects and COPD patients (Pi, M, MZ, and SZ); all had pulmonary function tests. We arbitrarily divided the group of 16 normal subjects at 2.7 units/mg Cp. The percent predicted FEV1 (86.2±9.4, N = 7) in the group with Cp activity <2.7 was significantly lower than the others (104.8±15.2, N = 9, p<0.02). These data suggested that high Cp activity may protect antiprotease, preserving lung elasticity and expiratory flow rates. To explore this further, we studied 23 patients with COPD separated into a group with higher (2.8±0.9) and lower (1.7±0.5) Cp function. The group with low CP activity was again divided using an arbitrary EIA level of 50%. The percent of predicted FEV1 was 15.0±3.8 (low Cp, low EIA, N =4), 29.2±11.8 (low Cp, high EIA, N = 7, p<0.03) and 35.6±16.5 (high Cp, N = 12, p<0.005). Percent predicted FEV1 is least abnormal in patients with higher Cp activity. In patients with depressed Cp function, those with the lowest EIA have the most abnormal FEV1. Low EIA was not related to the protease inhibitor phenotype. Family studies indicate that EIA and Cp activity at acid pH may be under genetic control. These observations suggest that EIA and Cp activity play a role in preventing lung injury. When EIA is low, the Cp activity may be critical in protecting the available EIA.

Abstract Highly selective cleavage of the human C3 molecule was produced by human leukocyte elastase (HLE). Limited digestion of C3 by HLE at a molar ratio of 20:1, pH 7.4, and room temperature released a low m.w. fragment from the α-chain of C3. This polypeptide has been identified as an analogue of C3a anaphylatoxin based on cross-reactivity with rabbit antihuman C3a. Chemical characterization by acrylamide gel electrophoresis, end group analysis and amino acid analysis identified the polypeptide as residues 1 to 71 of the 77 residue C3a molecule. The fragment of C3 released by HLE does not contract smooth muscle or induce a chemotactic response with rabbit polymorphonuclear leukocytes. More extensive digestion of C3 by HLE at 37°C produces four distinct fragments of the α-chain without cleavage of the β-chain. These four fragments have been designated α-1, α-2, α-3, and α-4 according to their relative migration in sodium dodecyl sulfate acrylamide gels.

Bencze, Sabatke and Fruhmann (see page 761) report a difference in the distribution of PiM subtypes in normal subjects and in patients with chronic bronchitis. They suggest that the PiM2 type predisposes carriers to chronic obstructive pulmonary disease (COPD) and therefore may be a useful test in deciding which workers can be exposed to noxious agents in industry.

Aprepitant, a substance P neurokinin-1 receptor antagonist, is licenced for the prevention of acute and delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy.A 33 year-old male with metastatic gastro-oesophageal cancer had multiple admissions for refractory nausea and vomiting following insertion of an oesophageal stent.Mechanical issues with the stent, stent removal and central causes were excluded. Multiple anti-emetic agents were trialled in combination and with varying routes of administration without significant symptomatic improvement.A trial of aprepitant was proposed as an off-licence therapy.One hundred sixty-five milligrammes of aprepitant was given orally every 3 days and then up titrated to once daily with significant symptomatic improvement enabling the patient to tolerate an oral diet. The patient remained stable at 12 weeks and has been accepted into two clinical trials for potential further cancer treatment.Aprepitant can be effective in refractory nausea and vomiting outside of emetogenic chemotherapy and safely used as a chronic treatment. The prevalence of refractory nausea and vomiting as a rare adverse outcome post-oesophageal stent insertion should be studied.Further research of neurokinin-1 inhibitors for indications other than chemotherapy-induced nausea and vomiting is indicated.

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CORRECTION article Front. Plant Sci., 22 November 2017Sec. Plant Pathogen Interactions Volume 8 - 2017 | https://doi.org/10.3389/fpls.2017.02012

The object of this dissertation is to study the structure of special types of Banach algebras which we have labeled convolution measure algebras.There are several important examples of such algebras.known whether the closure of H is proper in S' .The solution of the Shilov boundary problem may depend on the answer to this question.In Chapter V we list several unsolved problems which arise in connection with this work.v

452 BOOK REVIEWS meant the formal extrinsic cause, the causa exemplaris, but the intrinsic formal cause. To the present reviewer such a teaching seems very like theological pantheism. But Fr. Rahner is not worried by that; nor is he worried by the very formal and explicit teaching of the Council of Trent that the unique formal cause of justification is created grace (Denz. 799). He explains {or perhaps better, explains away) this explicit teaching of the magisterium by saying that " we must remember that the Council only wishes to meet the imputation theory of the Reformers, Seripando and others, but did not wish to determine how created and uncreated (inner!} grace (of which latter it also says precisely 'signans et ungens Spiritu promissionis Sancto . .') are related to each other and together constitute the single grace of justification" (p. 841-842}. In attributing his theory to St. Thomas (p. 888} Fr. Rahner again displays an amazing facility for reading into the words of the Angelic Doctor a meaning which is not to be found there. Examples of this kind could be multiplied almost without end. Let these three, however, suffice to give some idea of Fr. Rahner's theological method and teaching. They will also suffice to explain why we feel ourselves driven to the conclusion that Fr. Rahner, in the process of making theology " vividly alive," has only succeeded in making it less orthodox. Albertinum, Fribourg Switzerland. C. WILLIAMS, 0. P. St. Thorruu Aquinas, Commentary on the Metaphysics of Aristotle, Translated by JoHN P. RowAN, II Volumes; Henry Regnery Co. {1961} {$25.00) One who is requested to write a review of a translation, is given not one but two tasks. Obviously he is expected to record his comments on the merits of the translation. But there is another feature of the work about which he should express an opinion. It is this. Does the original merit a translation? It was with concern for the two tasks that .this reviewer approached the translation of St. Thomas, Commentary on the Metaphysics of Aristotle by John P. Rowan. Did Professor Rowan expend what must have added up to a very large investment of time, patience and scholarly research on a worthwhile project ? Or was his effort analogous to the groaning mountain that brought forth the mouse? M. Etienne Gilson, whose historical studies in Thomism have earned for him the right to be heard with respect, writes of the phil- BOOK .REVIEWS 458 osophical treatises: " Les Commentaries de S. Thomas sur AriStote sont pour nous des documents precieux, dont Ia perte eut ete deplorable." (Le Thomisme, 1948) . Whether one is in complete agreement with Gilson's description of their (happily contrary to fact) loss as "deplorable," or believes such an occurrence should merit a much stronger term, depends ultimately on his acceptance or rejection of Gilson's central thesis on the character of Thomism. · In a sense though Gilson's " deplorable " situation is· not entirely contrary to fact. In a manner of speaking. the Commentaries of St. Thomas on Aristotle are lost, and this in spite of the fact that copies of the same are to be found in full view: on the library shelves of Universities, Colleges and Seminaries. While physically available to anyone who wishes to take and read, they are not in the same measure intellectually available. Their thought remains remote, inaccessible because it lies beneath a language that is today ' deader ' than it was twenty years ago. But some adventurous souls were not content and translations of some of the Commentaries began to appear. For those, however, whose interest in philosophy brought them to Metaphysics, these translations have served to heighten the sense of loss at the remoteness of St. Thomas' Commentary on· the Metaphysics. Nor was the attempt to assuage the feeling of loss by pointing out the availability of Aristotle's text in the vernacular too successful . The fact is that these translations of Aristotle's text offer the student the thought of Aristotle in a language that is familiar but that thougkt remains difficult to grasp. The metaphysical thought of Aristotle, and to a degree the thought of the entire Corp'UIJ A:ristotelicum, demands a...

BOOK REVIEWS 171 seems to have brought the best insight to his work. Thirty-two pages -of illustration make the study on architecture attractive. Bibliographers may be excused for over-praising the two volume Bibliography . It serves not only those seeking books on religion but is also an equerry to readers in related·fields. In it a surprisingly large number of dissertations and studies on Catholic education is noted. Peter Guilday's Life and Times of· Jokn England is called the finest biography of an American Roman Catholic bishop. However , some Catholic encyclopedias seem to have been omitted, along with some basic American Catholic biographical work. The section " Religion and the Intellectuals " seems quite thin. Some Catholic (or other!) graduate historical seminar could consider what is pointed out on page 1042 in the second book of the Bibliography: "The History of Roman Catholic Seminaries in the United States-still lacks a scholarly and comprehensive work." It might also be noted that in the two essays concerning theology, no attempt is made to assay Catholic theology, either in historical survey or to judge its conclusions. This fact seems to indicate that at least there should. be a beginning survey of Catholic theology in the United States done by some competent scholar or group. In sum, all who hold religion to be vital to the United States are in debt to the editors and authors of Religion in American Life. Providence OoUege, Providence, B. I. DANIEL F. R.EILLY, O.P. Anselm: Fidea Q'IUBrens InteUectum. KAiu. BARTH. Richmond, Va.: John Knox Press, 1960. Pp. 178. $8.00. Anselm: Fidea Qurerens lntellectum offers us Karl Barth's study of Saint Anselm's search and discovery of what was to his mind an irrefutable proof of God's Existence. The author confesses to a continued interest in Saint Anselm, the theologian, particularly in the context of his famous proof. The work, which is the second edition of a study originally made in 1981, fulfills a twofold purpose. In the preface to the first edition Barth explains the work as an apologia for his great interest in this catholic theologian whose merit, he claims, has never been fully understood and appreciated. But the thought of Saint Anselm also exercises its own attraction. " From all this I cannot deny that I deem Anselm's Proof of the Existence of God in the context of his theological Scheme a model piece of good, penetrating and neat theology, which at every step I have found instructive and· edifying " (p. 9) . Underlying Barth's study and becoming more and more 17~ BOOK REVIEWS apparent with the progress of the work is the conviction that the so-called ontological proof, a description he strongly resents (p. 171), has been almost always wrenched from its proper setting and made to appear in a false garb. Throughout the work Barth, whether wittingly or not, tends to create the impression that no one, besides himself, ever approached the ansehnian proof sympathetically, that the interest of others was to disprove rather than to understand. His attitude towards catholic theologians seems to proceed from such an assumption and from time to time he lends credence to this suspicion by the curtness with which he refers to them. Frequently he seems to question their appreciation of theology in rejecting Saint Anselm's proof, rather than the grounds upon which they do reject the argument. Surely, it would be more acceptable to presume that any theologian would be moved sympathetically towards every argument purporting to prove the Existence of God. And if a proof be rejected, it could be licitly assumed that the rejection was based not on the absence of sympathy on the part of the theologian, but on the insufficiency, real or apparent, of the proof. The very failure to approach Saint Ansehn with sympathy which he charges and decries in other theologians, is perceptible in his approach to them. The study itself of Saint Ansehn's Proof begins with a rather extended treatise on the Theological Scheme which constitutes the framework of the Proof. In it Barth discusses the nature and necessity of theology, its possibility and aim. In his description of theology...

This book deals with the topic of pulmonary emphysema. Included are the following chapters: Abnormality of secretion of Z Alpha-1-antitrypsin, Proteases, antiproteases, and oxidants in the pathogenesis of pulmonary emphysema, Alveolar Leukocytes and protease responses with continuous vs. intermittent exposures to NO{sub 2}.

Space Physics with Artificial Satellites. By Ya. L. Al'pert, A. V. Gurevich and L. P. Pitaevskii. Translated from Russian by H. H. Nickle. Consultants Bureau, N.Y.1965. 240 pp. $25.00. - Volume 1 Issue 3

An α1 protease inhibitor which is sensitive to increased temperatures and which migrates in the same position as the normal M1 phenotype, has been identified. The sensitivity of the trypsin inhibitory capacity is an inherited characteristic, which is enhanced by acid conditions, as well as conditions during isoelectric focusing. Loss of the serum trypsin inhibitory capacity is not parallel to that of the serum elastase capacity, suggesting that the inhibitory sites for these pro teases are oriented differently within the α1 protease inhibitor molecule.

The effect of porcine pancreatic elastase and mechanical ventilation on tissue elastic recoil was examined in excised dog lung lobes. Lobes incubated for one hour with an elastase-buffer mixture showed a significant (P less than 0.001) left shift of the liquid-filled pressure-volume curve at all pressures measured (0 to 12 cm H2O) when compared to lobes treated with buffer only. These results suggest that the contribution of elastin to the elastic properties of lung tissue is greatest at mid-lung volumes, but that it also contributes to delimiting maximal lung volume. Elastase and buff-treated lobes were inflated cyclically with humidified air to a pressure of 20 cm H2O 6 times per min during a 16-hour period. This mechanical ventilation caused no further decrease of tissue elastic recoil. Ventilation did cause an unexpected increase in the elastic recoil of liquid-filled lobes that was significant at pressures of 4 cm H2O (P less than 0.025) or more (P less than 0.001). Elastase and buffer-treated lobes showed an almost identical rightward shift of the pressure-volume curve after ventilation when compared to the respective nonventilated control lobes. This increased recoil cannot be attributed to altered surface tension.

The current aim of our laboratory is to identify, to quantitate and to determine the relationship of plasma antioxidants to α1 protease inhibitor (α1Pi) and elastase in chronic obstructive pulmonary disease (COPD). These studies are a consequence of the growing body of evidence suggesting that oxidative destruction of the elastase inhibitory capacity (EIC) of α1Pi in the lung may be an important pathogenetic mechanism in emphysema. 1 Janoff A, Carp H, Laurent P, Raju L. The role of oxidative processes in emphysema. Am Rev Respir Dis (in press) Google Scholar Myeloperoxidase (MPO) in the presence of Cl− and H2O2, cigarette smoke oxidants and environmental oxidants such as ozone can directly inactivate the EIC of α1Pi. 2 Matheson NR Wong PS Travis J Enzymatic inactivation of human alpha1 proteinase inhibitor by neutrophil myeloperoxidase. Biochem Biophys Res Commun. 1979; 88: 402-409 Crossref PubMed Scopus (182) Google Scholar , 3 Carp H Janoff A Possible mechanisms of emphysema in smokers. In vitro suppression of serum elastase inhibitory capacity by fresh cigarette smoke and its prevention by antioxidants. Am Rev Respir Dis. 1978; 118: 617-621 PubMed Google Scholar , 4 Johnson DA Ozone inactivation of human α1-proteinase inhibitor. Am Rev Respir Dis. 1980; 121: 1031-1038 PubMed Google Scholar The inhibitory function of the molecule can be protected by antioxidants. For example, we found that ceruloplasmin, the major antioxidant of plasma, inhibits the enzymatic inactivation of α1Pi. 5 Taylor JC Oey L Ceruloplasmin: Plasma inhibitor of the oxidative inactivation of alpha 1 protease inhibitor. Am Rev Respir Dis. 1982; 126: 476-482 Google Scholar We also have reported the existence of a potential abnormality in this antioxidant system in COPD patients. 6 Taylor JC Properties of human granulocyte elastase from normal subjects and patients with chronic obstructive pulmonary disease. in: Havemann K Janoff A Neutral proteases of human polymorphonuclear leukocytes. Urban & Schwarzenberg, Baltimore-Munich1978: 129-135 Google Scholar , 7 Martin II, WJ Thylor JC Abnormal interaction of alpha1 antitrypsin and leukocytic elastase activity in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1979; 120: 411-419 PubMed Google Scholar