tbuckley/cabot-search huggingface dataset:
S129 A two species proteomics approach to determine MMP-12 substrates in COPD
Authors: B Mallia-Milanes, A Dufour, H Bailey, G Meakin, A Leme, C Bolton, S Shapiro, C Overall, S Johnson
Journal: Thorax (2015)

<h3>Background</h3> Genetic variability in MMP-12 is associated with COPD; the matrix Metalloproteinase (MMP)-12 knockout (KO) mouse is resistant to emphysema despite cigarette smoke exposure, strongly implicating MMP-12 in COPD pathogenesis. However, the complete MMP-12 substrate profile (degradome) in COPD remains unknown. Terminal amine isobaric labelling of substrates (TAILS) is a novel proteomic technique allowing identification of a protease degradome on an organism-wide scale. Identification of the MMP-12 degradome will lead to novel drugs, desperately needed in COPD. <h3>Objectives</h3> To identify the MMP-12 degradome in COPD by comparing cigarette smoke exposed MMP-12 KO and wildtype (WT) controls by TAILS and validating these targets against the human COPD sputum proteome during exacerbations and stable disease. <h3>Methods</h3> C57BL/6J MMP-12 KO and WT mice (n = 4) were exposed to cigarette smoke and airways sampled by bronchoalveolar lavage (BAL). BAL fluid was analysed by TAILS, high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS). Matched COPD exacerbation and stable disease sputum samples (n = 9) were analysed by TAILS, HPLC and MS/MS. <h3>Results</h3> The following new MMP-12 targets in the COPD mouse model were identified: alpha-2-HS glycoprotein, anti-thrombin III, clusterin, complement C3, complement C4b, complement factor H-related protein-1, hemopexin, serotransferrin and serum albumin, alpha-2-macroglobulin, beta-1, 4-galactosyltransferase 2, transmembrane protease 7, DEP domain-containing mTOR-interacting protein, kininogen-1, tumour necrosis factor ligand superfamily member 11. Of these, alpha-2-HS-glycoprotein, anti-thrombin III, complement factors C3 and C4B, hemopexin and serum albumin were identified in both exacerbation and stable COPD human sputum. Furthermore, 1,116 peptides were identified in COPD exacerbation and stable disease sputum, grouped into the following categories: cell adhesion/migration, complement system, acute phase response, extracellular matrix structure/function, anti-microbicidal activity, cytoskeletal function/remodelling, carbohydrate metabolism, oxidoreductase activity, cell death regulation/DNA synthesis/repair, immune response, protease activity, protease inhibition and ATP synthesis/function. <h3>Conclusion</h3> This study identifies the MMP-12 degradome in COPD and provides the most comprehensive analysis of the proteome of COPD sputum at exacerbation and stable disease. It suggests a role for MMP-12 in complement regulation and haemostasis in COPD. Thus an important peptide library has been unravelled, providing an ideal tool in developing drugs and understanding COPD pathogenesis.
<i>Pseudomonas aeruginosa</i>Epidemic Traced to Delivery-Room Resuscitators
Authors: Joshua Fierer, Paul M. Taylor, Horace M. Gezon
Journal: New England Journal of Medicine (1967)

THE incidence of infection with Pseudomonas aeruginosa, ordinarily an indifferent pathogen, is apparently rising in adult and pediatric patients1 , 2 in this country and in England.3 Premature infants are particularly susceptible to such infections,4 , 5 and, in them, disease is marked by a high case-fatality ratio. Therefore, prevention of infections in the nursery is of prime importance. It is hoped that this will be accomplished when the epidemiology of pseudomonas infections in nurseries is more clearly delineated.The epidemic described in this report occurred in a premature nursery in which Ps. aeruginosa was initially isolated from several environmental sites, none of . . .
Carcinoma of the Bladder
Authors: Fletcher H. Colby, Walter S. Kerr
Journal: New England Journal of Medicine (1951)

RECENT years have seen an increasing tendency to treat cancer of the bladder by radical methods. The present seems to be the time to evaluate our long-term results of total cystectomy and to determine whether the removal of the diseased bladder has resulted in a significantly higher long-term survival rate than have other less formidable procedures. In particular, the indications for total cystectomy seem to require clarification.From 1934 to 1950, 103 total cystectomies for cancer of the bladder were performed at the Massachusetts General Hospital. The results up to the present time are known in all these cases. Seventeen . . .
Propylthiouracil and Transfusion Modifications of the Effects of the Rauscher Virus in BALB/c Mice
Authors: Thelma B. Dunn, Richard A. Malmgren, Paula G. Carney, Arleigh W. Green
Journal: JNCI Journal of the National Cancer Institute (1966)

Groups of mice inoculated with the Rauscher virus were treated with different substances to determine whether the characteristic erythroblastic reaction and the survival time could be altered when compared with those of untreated virus-inoculated controls. The feeding of liver, injection of vitamin Brt or folic acid, administration of chloramphenicol or ferrous sulfate, thyroidectomy, or bleeding proved ineffective under the conditions of the trials. Propylthiouracil added to the food of virus-inoculated mice prolonged life and altered the morphology of the spleen. Repeated blood transfusions inhibited the erythroblastic reaction and prolonged the survival time. One mouse given a transfusion showed an extreme proliferation of erythroblastic stem cells and another a proliferation of granulocyte stem cells. A glomerular lesion was noted frequently in the mice fed propylthiouracil and in one mouse given blood transfusions.
Tracheoesophageal Fistula Unassociated with Atresia or Stenosis: Difficulties in Diagnosis and Suggestions for Greater Accuracy
Authors: Hugo M. Cardullo, David L. Berens
Journal: New England Journal of Medicine (1950)

CONGENITAL tracheoesophageal fistula without esophageal atresia has rarely been diagnosed in the first few days of life. This case reported below is presented to demonstrate that the condition does exist and can be diagnosed early and that detection of a small fistula may be enhanced by the use of an aqueous contrast medium instead of oil.Case ReportR. B. (B.H. 6386–50), the firstborn son of normal young parents, was transferred to the Children's Medical Service from another hospital at 48 hours of age with a diagnosis of "pneumonia and possible esophageal atresia." From the first feeding, 12 hours after . . .
Reduction of Colonic Carcinogenesis by Wheat Bran Independent of Fecal Bile Acid Concentration&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: R J Calvert, D M Klurfeld, S Subramaniam, G V Vahouny, D Kritchevsky
Journal: JNCI Journal of the National Cancer Institute (1987)

It has been reported previously that populations with a decreased concentration of fecal bile acids have a lower incidence of colon cancer. We examined the importance of fecal bile acid dilution by wheat bran (WB) in inhibiting colonic tumorigenesis in an experimental animal model. Male F344 rats received oral doses of the colon carcinogen 1,2-dimethylhydrazine [CAS: 540-73-8] and were assigned randomly to groups fed one of four semipurified diets for 26 weeks. The diets were fiber-free (FF), 10% WB, FF + bile salts, or WB + bile salts. The amount of bile salts added was adjusted to produce a fecal bile acid concentration in the group fed WB + bile salts equal to that found in the FF groups. Fecal bile acid concentrations at 12 and 24 weeks in the WB + bile salts group were similar to those in the FF group. Gross and microscopic findings at necropsy revealed a reduced total number and multiplicity of colon tumors in both bran-fed groups. Although the fecal bile acid concentrations of the FF and WB + bile salts groups were equal, the latter showed a significant reduction in tumor yield.
Concordance with NCCN Colorectal Cancer Guidelines and ASCO/NCCN Quality Measures: An NCCN Institutional Analysis
Authors: Dorothy Romanus, Martin R. Weiser, John M. Skibber, Anna Ter Veer, Joyce C. Niland, John L. Wilson, Ashwani Rajput, Yu-Ning Wong, Al B. Benson, Stephen Shibata, Deborah Schrag
Journal: Journal of the National Comprehensive Cancer Network (2009)

The National Comprehensive Cancer Network (NCCN) Outcomes Database was created to assess concordance to evidence- and consensus-based guidelines and to measure adherence to quality measures on an ongoing basis. The Colorectal Cancer Database began in 2005 as a collaboration among 8 NCCN centers.Newly diagnosed colon and rectal cancer patients presenting to 1 of 8 NCCN centers between September 1, 2005, and May 21, 2008, were eligible for analysis of concordance with NCCN treatment guidelines for colorectal cancer and with a set of quality metrics jointly developed by ASCO and NCCN in 2007. Adherence rates were determined for each metric. Center-specific rates were benchmarked against mean concordance rates for all participating centers.A total of 3443 patients were evaluable. Mean concordance rates with NCCN colorectal cancer guidelines and ASCO/NCCN quality measures were generally high ( >or= 90%). However, relatively low mean concordance rates were noted for adjuvant chemotherapy treatment recommendations within 9 months of diagnosis of stage II to III rectal cancer (81%), and neoadjuvant chemoradiation in clinical T4 rectal primaries (83%). These low rates of concordance seemed to be consistent across centers.Adherence to guidelines and quality measures is generally high at institutions participating in the NCCN colorectal cancer database. Lack of documentation, patient refusal, delayed treatment initiation, and lack of consensus about whether treatment was essential were the primary reasons for nonconcordance. Measurement of concordance and the reasons for nonconcordance enable participating centers to understand and improve their care delivery systems.
Incremental value of 3D echocardiography and two-dimensional speckle tracking in the early detection of cardiotoxicity linked to chemotherapy and trastuzumab in patients with HER-2 positive breast cancer
Authors: L. Conte, I. Fabiani, N.R. Pugliese, C. De Angelis, I. Bertolini, I. Ferrarini, S. Fancelli, A. Fontana, B. Salvadori, E. Landucci, A. Michelotti, A. Falcone, V. Di Bello
Journal: Annals of Oncology (2015)
Risperidone for treatment-refractory schizophrenia
Authors: T B Tanner, R Ganguli, R Reddy, M Allen, K Field
Journal: American Journal of Psychiatry (1995)

Marder and Meibach reported a 46%-SS% chance (depending on dose level) of patients finishing an 8-week trial of risperidone. We also observed that there was a large proportion of patients for whom risperidone therapy was not beneficial. Of the 33 schizophrenic patients prescribed risperidone, 10 (30%) discontinued the medication after an average trial length of 14 weeks. The remaining 23 patients (70%) are being prospectively studied (current trial length is 14 weeks). Lack of clinical response explained seven of the 10 failures. Other reasons were noncompliance (N=2) and skin rash (N=1). We report a representative case of the ineffectiveness of risperidone for a patient who was resistant to standard neuroleptic treatment.
Mumps-Virus Infection in Pregnant Women and the Immunologic Response of Their Offspring
Authors: Jon M. Aase, George R. Noren, D. Venudhar Reddy, Joseph W. St.Geme
Journal: New England Journal of Medicine (1972)

Twelve Eskimo children were evaluated 10 years after intrauterine exposure to mumps virus. The mothers of all 12 gave serologic evidence of having been exposed to mumps virus, as did nine older children born before the epidemic (these nine also had positive mumps skin tests). None of the 12 children conceived during the epidemic had mumps-virus neutralizing antibodies, and 10 of 12 had positive mumpsvirus skin tests. Of 32 children born after the epidemic 31 were negative for mumps-virus neutralizing antibody whereas six had a positive mumps skin test. Exposure of the embryo or fetus to mumps virus therefore seems to have evoked immunologic recognition that persisted into childhood. The immunologic response was primarily cellular and manifested by delayed hypersensitivity.
Acute Febrile Neutrophilic Dermatosis in Acute Myelogenous Leukemia
Authors: M Starobinski, D Salomon
Journal: New England Journal of Medicine (1998)

Figure 1. Several erythematous nodules and papulopustules developed on the arms (Panel A), upper legs, and face of a 57-year-old man, accompanied by a fever (temperature as high as 40°C) despite treatment with broad-spectrum antibiotics and amphotericin B, during chemotherapy with cytarabine and idarubicin for acute myelogenous leukemia type M4 according to the French–American–British system of classification. On day 7 of induction therapy, the patient's white-cell count was 500 per cubic millimeter and a biopsy showed a dense infiltrate of neutrophils (arrowheads in Panel B) and mononuclear cells around the sweat glands that extended into the adipose tissue (the letter . . .
Optimum End-Expiratory Airway Pressure in Patients with Acute Pulmonary Failure
Authors: Peter M. Suter, H. Barrie Fairley, Michael D. Isenberg
Journal: New England Journal of Medicine (1975)

To determine whether in the management of pulmonary failure, the maximum compliance produced by positive end-expiratory pressure coincides with optimum lung function, 15 normovolemic patients requiring mechanical ventilation for acute pulmonary failure were studied. The end-expiratory pressure resulting in maximum oxygen transport (cardiac output times arterial oxygen content) and the lowest dead-space fraction both resulted in the greatest total static compliance. This end-expiratory pressure varied between 0 and 15 cm of water and correlated inversely with functional residual capacity at zero end-expiratory pressure (r equal -0.72, p less than or equal to 0.005). Mixed venous oxygen tension increased between zero end-expiratory pressure and the end-expiratory pressure resulting in maximum oxygen transport, but then decreased at higher end-expiratory pressures. When measurements of cardiac output or of true mixed venous blood are not available, compliance may be used to indicate the end-expiratory pressure likely to result in optimum cardiopulmonary function.
Pope should be doctors' hero
Authors: C A Crowther
Journal: BMJ (1996)

EDITOR,—As a balance to the editorial calling Jack Kevorkian a medical hero1 I wish to suggest another hero, conscious that my offering may be less acceptable to readers. This hero makes many people feel uncomfortable; he speaks relentlessly and courageously about the value and dignity of human life. He is also a man of action, and wherever he travels he seeks out sick, disabled, and vulnerable people and stands compassionately with them. My suggested hero is Pope John Paul …
Chromosomal Studies of Patients with Congenital Anomalies Simulating Those of Gonadal Aplasia
Authors: Kiyoshi Oikawa, Robert M. Blizzard
Journal: New England Journal of Medicine (1961)

PERSONS with gonadal aplasia, also called Turner's syndrome,1 Bonnevie–Ullrich syndrome2 and ovarian agenesis,3 are apparent females who consistently have short stature and sexual infantilism.4 , 5 In addition they frequently have other multiple congenital anomalies. Haddad and Wilkins5 recently reviewed the nonsexual abnormalities of 55 females with this syndrome. A high percentage of these patients had a combination of anomalies, including a shield-like chest, micrognathia, epicanthal folds, high palate, low-set ears, webbed neck, hypoplastic nails, idiopathic hypertension, lymphedema of the hands and feet, cutis laxa, keloid formation, mental retardation and deafness.The cause of the short stature remains unexplained. However, the sexual . . .
Towards understanding the role of autoreactivity in COPD
Authors: Ted Mes, Theo Bijma, Martijn Nawijn, Corry-Anke Brandsma, Dick Bonarius, Marlies van Dijk, Huib Kerstjens, Wim Timens
Journal: European Respiratory Journal (2011)

The role for autoimmunity in the pathogenesis of COPD is controversial, and the identity of putative autoantigens is subject to debate. In order to examine the role for autoantibodies in COPD, we cloned the complete variable light and heavy chains from single-cell sorted IgG or IgA-positive activated memory B cells isolated from COPD and control lung tissue, and expressed these as complete human Ig monoclonal antibodies (HumAbs). These HumAbs were tested for autoreactivity by histology using lung tissue sections of COPD patients and healthy controls and lung cell lines. In addition, serum of COPD patients and healthy controls was used to determine binding of antibodies to epithelial, fibroblast, and endothelial cell lines.  The HumAbs stained multiple cells and structures in lung tissue sections such as smooth muscles cells, epithelial cells, and the adventitia. The cell lines examined thus far, two epithelial cell lines, were also stained by the HumAbs.  Serum IgA and IgG antibody titers against epithelial, fibroblast, and endothelial lung cell lines overlapped considerably between patients and controls. As a consequence, the differences between titers of patients and controls were marginally significant. Interestingly, however, some COPD patients had a high serum antibody titer against one cell line, but a low titer against another cell line. Our results illustrate the complexity of autoreactivity in COPD in that concomitant with the preferential binding of different types of lung cells by antibodies in serum of COPD patients, individual antibodies may also target multiple cells and structures in the lung.
Bananas as a Low-Sodium Dietary Staple
Authors: Warren E. C. Wacker, Marvin Margoshes, Anthony F. Bartholomay, Bert L. Vallee
Journal: New England Journal of Medicine (1958)

THE ubiquitous distribution of sodium in foodstuffs has presented difficulties in the preparation of suitable dietary regimens for patients affected with salt-retaining conditions like congestive heart failure, cirrhosis of the liver and nephrotic syndrome. The low-sodium diets that have been used in the past, such as the rice diet,1 have not gained wide acceptance, probably because of their monotonous unpalatability. A readily available staple, palatable, low-sodium food would be a useful dietary adjunct in the treatment of these salt-retaining states.The banana is a food that seemed to fit these requirements, since its sodium content had been reported to be . . .
Chemotherapy for Advanced, Recurrent, and Metastatic Cervical Cancer
Authors: David H. Moore
Journal: Journal of the National Comprehensive Cancer Network (2008)

When cervical cancer is beyond curative treatment with surgery or radiation therapy, the prognosis is poor and palliation is the primary objective. Early prospective studies identified cisplatin as an active drug for advanced, metastatic, or recurrent cervical cancer, and results with other platinum analogs seemed inferior to cisplatin. Several phase III trials have established the combination of cisplatin plus paclitaxel as standard therapy for comparison. Using pooled data from 3 Gynecologic Oncology Group (GOG) phase III studies, a predictive model was developed to better identify patients who are unlikely to respond to cisplatin-containing chemotherapy. The GOG is currently developing a phase III trial to investigate the impact of bevacizumab and a regimen containing topotecan instead of cisplatin in combination with paclitaxel chemotherapy and also to externally validate the predictive model. This study has the potential to radically change standard care for cervical cancer chemotherapy. Furthermore, if the predictive model is upheld, then patients with high risk factors for treatment failure may be directed to chemotherapy regimens that do not include cisplatin or to investigational trials.
FRI0297 Risk Factors of Lumbar Spine Osteoporosis in RA Patients
Authors: E. Taskina, L. Alekseeva, P. Dydykina, E. Petrova, N. Dyomin, A. Smirnov, I. Dydykina, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rate of vertebral body fractures and spinal deformities is 2-fold higher in RA patients compared to general population, compromising their quality of life. <h3>Objectives</h3> To identify major risk factors of lumbar osteoporosis (OP) in RA female patients. <h3>Methods</h3> The study included 220 RA female patients (ACR criteria), aged 20-75 y. (mean age – 57,1±10,8 y). An individual patient9s file contained anthropometric parameters, social and demographic data, case history, clinical examination and lab findings, traditional OP risk factors, patient9s joint status, info on concurrent diseases, pain intensity evaluation by VAS and evaluation of general health status. Bone mineral density (BMD) was measured using DEXA scan. DEXA T-score was used in post-menopausal women, and Z-score - in menstruating women. <h3>Results</h3> Patients were grouped in two arms: patients with lumbar spine OP – 74 (33,6%) and without OP in the lumbar spine – 146 (66,4%). OP patients were somewhat older (59,8±10,2 vs 56±11,1 y., <i>p</i>=0,02 respectively), greater extent of functional impairment (HAQ &gt;2) (43,4 vs 29,5%, RR =1,47, 95% CI 0,98–2,21, <i>p</i>=0,05), longer use of glucocorticosteroids (GC) (72 (36–110) vs 50 (12–95) mo, <i>p</i>=0,05), and at higher average daily doses during the previous year (6,3 (2,5–8,75) vs 5 (2,5–7,5) mg/day., <i>p</i>=0,01), as well as higher total GC dose 14,4 (5,4–25,8) vs 9 (2,4–16,5) g, <i>p</i>=0,02). RA activity by DAS28 and current radiographic lesions (Van der Heijde modification of Sharp method) was comparable in both groups. Analysis of traditional OP risk factors identified lower body weight in OP patients (64,4±10,6 vs 69,2±12,9 kg, <i>p</i>=0,01) and post-menopause status in the majority of them (94,6 vs 74%, RR =1,28, 95% CI 1,14–1,42, <i>p</i>=0,0001). Discriminate analysis identified the following major lumbar spine OP risk factors: RA duration, severe functional impairment by HAQ, average GC daily dose in the previous year and menopause. Based on identified factors and their coefficients a model was suggested (with area under the curve – AUC- equal to 0,784), allowing to predict lumbar spine OP with high precision, equal to 74.5%. <h3>Conclusions</h3> Lumbar spine OP in RA female patients is to great extent predetermined by RA duration, higher degree of functional impairment by HAQ, average daily GS dose in the previous year and the menopause status. <h3>Disclosure of Interest</h3> None declared