tbuckley/cabot-search huggingface dataset:
PHYLOGENY OF IMMUNOGLOBULIN STRUCTURE AND FUNCTION
Authors: Gerrie A. Leslie, L. W. Clem
Journal: The Journal of Experimental Medicine (1969)

Chicken 7.1S immunoglobulin was purified from whole chicken serum by DEAE-cellulose chromatography and Sephadex G-200 gel filtration. The macroglobulin was purified by a combination of salt precipitation and Sephadex G-200 gel filtration. Both immunoglobulin molecules yielded 75% heavy (H) chains and 25% light (L) chains when subjected to extensive reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. Antigenically reactive H and L chains were obtained by partial reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. The 7.1S and 16.7S immunoglobulin H chains were antigenically unrelated to each other, whereas the L chains were antigenically indistinguishable from one another. The 16.7S H chains were found to have a mass of approximately 70,000, and the 7.1S H chains had a mass of 67,500. The mass of the L chains was approximately 22,000. Sedimentation equilibrium studies of the 7.1S immunoglobulin molecule gave a mol wt of approximately 170,000 which is in good agreement with the 179,000 predicted on the basis of 2 H and 2 L polypeptide chains. The 16.7S molecule was shown to have a mol wt of approximately 890,000. A reductive subunit that has a mol wt of approximately 174,000 has been isolated from the 16.7S molecule. These values are consistent with the chicken macroglobulin having five subunits, each of which has 2 H and 2 L chains. The hexose contents of the chicken 7.1S and 16.7S immunoglobulins are 2.2% and 2.6%, respectively. The extinction coefficients of the 7.1S and 16.7S immunoglobulins were 13.18 +/- 0.04 and 12.72 +/- 0.77, respectively, when measured in 0.3 M KCl. Based upon physical-chemical and antigenic characteristics, the 16.7S immunoglobulin most closely resembles IgM of mammals. The 7.1S immunoglobulin definitely belongs to a different class than the 16,7S immunoglobulin, but it does not align itself very well with any of the mammalian immunoglobulins. We propose that this molecule be designated as IgY. Furthermore, this designation would be useful for the immunoglobulins of other species for which there is insufficient correlation with any of the known human immunoglobulins.
Possible Overuse of 3-Stage Procedures for Active Ulcerative Colitis
Authors: Caitlin W. Hicks, Richard A. Hodin, Liliana Bordeianou
Journal: JAMA Surgery (2013)

There is an assumption that patients treated with 3-stage procedures for active ulcerative colitis are undergoing a safer surgical approach and thus spared the complications associated with a 2-stage procedure. However, there is a paucity of data addressing the validity of this assumption, and the optimal staging approach for patients traditionally considered at high risk for anastomotic leak remains unclear.To identify factors associated with 3- vs 2-stage procedures and to determine their impact on surgical outcomes.Retrospective analysis of patients who underwent 2-stage or 3-stage ileal pouch-anal anastomosis (IPAA) surgery for active ulcerative colitis due to failure of medical management over a 10.5-year period (September 1, 2000, to March 30, 2011). The mean (SEM) follow-up was 5.15 (0.24) years (range, 0.26-11.09 years).Single large academic medical center.One hundred forty-four patients treated with 3- or 2-stage IPAA surgery for active ulcerative colitis. Among these patients, 77 were male and 67 were female. The mean (SEM) age was 34.6 (1.0) years (range, 11-67 years). Of the 144 patients, 116 (80.6%) had a 2-stage procedure and 28 (19.4%) had a 3-stage procedure.Two-stage vs 3-stage IPAA procedures for active ulcerative colitis.Factors leading to decision for 3-stage procedure, postoperative outcomes with 3-stage vs 2-stage procedures, and risks for complications in patients undergoing 3-stage vs 2-stage procedures. RESULTS Of 144 patients, only 19.4% had a 3-stage procedure. Decision to perform a 3-stage vs 2-stage procedure was affected by emergent status (P < .001) and hemodynamic instability (P = .04) but not by age, sex, body mass index, use of steroids, or use of anti-tumor necrosis factor agents. For patients with 2-stage procedures, multivariate regression revealed that the number of perioperative complications was affected by surgeon experience (P = .02) but not by emergent status, use of steroids, or use of anti-tumor necrosis factor agents. Two-stage procedures were associated with more perioperative complications on univariate analysis (P = .05), but multivariate regression suggested that this difference was due to surgeon experience (P = .02) rather than to creation of an IPAA at the first operation (P = .55). Importantly, 2-stage procedures did not change the risk of anastomotic leak when all operations were taken into account (odds ratio = 1.09; P = .94). In the long term (mean [SEM], 5.2 [0.2] years), patients who underwent 2-stage surgery had a lower risk of anal stricture (odds ratio = 8.21; P = .01) and no differences in fistula or abscess formation or in pouch failure.In patients with active ulcerative colitis, use of steroids and anti-tumor necrosis factor agents alone do not appear to justify the decision to avoid IPAA creation at the first operation provided that it is performed by a high-volume inflammatory bowel disease surgeon.
The significance of the 'dust-like particles' pattern of immunofluorescence. A study of 66 cases
Authors: None Lipsker, None DI Cesare, None Cribier, None Grosshans, None Heid
Journal: British Journal of Dermatology (1998)

Subacute cutaneous lupus erythematosus (SCLE) is a marker of a unique subset of lupus erythematosus patients. A 'dust-like particles' direct immunofluorescence (DIF) staining pattern, which consists of fine granular particles of immunoglobulin(s) scattered through the epidermis and the cellular infiltrates of the dermis, was reported to be specific for SCLE. In this study, we assessed the real specificity of this staining pattern, which had not yet been evaluated. We systematically searched for the dust-like particles staining pattern among the 4374 skin biopsy specimens submitted for direct cutaneous immunofluorescence during a 7-year period (1989-96). The corresponding patient records were reviewed. Dust-like particles were observed in 66 samples originating from 60 patients. Only 53% of the patients had SCLE. The remaining patients had systemic lupus erythematosus with visceral involvement (17%), discoid lupus erythematosus (3%), mixed connective tissue disease (2%). Sjögren syndrome (2%) and other diseases. Eighty-five per cent of the patients had connective tissue disease. Seventy-seven per cent of the patients were positive for antinuclear antibodies, but only 36% were positive for anti-Ro (SSA) antibodies. This study shows that the dust-like particles staining pattern is not specific for SCLE, but is highly suggestive of connective tissue disease. The nature of the antigen responsible for the immunoglobulin deposition and the prognostic significance of this DIF pattern remain to be established.
Massive retrosternal goitre presenting with hypertension
Authors: M. P. Holden, G. H. Wooler, M. I. Ionescu
Journal: Thorax (1972)

A patient presented to her doctor with dyspnoea on exertion. Hypertension was diagnosed and she was subsequently found to have a large retrosternal goitre. The blood pressure returned to normal after the tumour had been removed. To our knowledge no such case has previously been reported. Early removal of mediastinal tumours is advocated.
Safety of Food Allergy Clinical Trials: The Consortium for Food Allergy Research's 10 Years of Experience
Authors: Robert W. Lindblad, Peter Dawson, Robert A. Wood, Alice Henning, Scott H. Sicherer, Tamara T. Perry, Stacie M. Jones, Brian P. Vickery, A. Wesley Burks, Andrew H. Liu, Donald Y.M. Leung, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2015)
Repeated allergen exposure of sensitized Brown-Norway rats induces airway cell DNA synthesis and remodelling
Authors: M. Salmon, D.a. Walsh, H Koto, P.j Barnes, K.f Chung
Journal: European Respiratory Journal (1999)

Chronic inflammation in asthmatic airways can lead to characteristic airway smooth muscle (ASM) thickening and pathological changes within the airway wall. This study assessed the effect of repeated allergen exposure on ASM and epithelial cell deoxyribonucleic acid (DNA) synthesis, cell recruitment and airway wall pathology. Brown-Norway rats were sensitized and then exposed to ovalbumin or saline aerosol every 3 days on six occasions. After the final exposure, rats were administered twice daily for 7 days with the DNA S-phase marker bromodeoxyuridine (BrdU). Using a triple immunohistochemical staining technique, BrdU incorporation into ASM and epithelium was quantified employing computer-assisted image analysis. There were &gt;3-fold mean increases in BrdU incorporation into ASM from 1.3% of cells (95% confidence interval (CI) 1.0-1.6) in saline controls to 4.7% (95% CI 2.6-6.7) after allergen exposure (p&lt;0.001), and in airway epithelium, from 1.3 (95% CI 0.6-2.0) BrdU-positive cells x mm basement membrane(-1) in saline controls to 4.9 (95% CI 3.0-6.7) after allergen exposure (p&lt;0.001). There was increased subepithelial collagen deposition and mucus secretion along with a significant eosinophil and lymphocyte recruitment to the airways. Increased rates of deoxyribonucleic acid synthesis in both airway smooth muscle and epithelial cells along with changes to the airway wall pathology may precede the establishment of smooth muscle thickening and airway remodelling after repeated allergen exposure in rats. This model seems to be appropriate for studying structural changes within the airways as observed in asthma.
Psoriatic arthritis treatment and the risk of herpes zoster
Authors: D Zisman, H Bitterman, G Shalom, I Feldhamer, D Comanesther, E Batat, S Greenberg-Dotan, S Cohen, A D Cohen
Journal: Annals of the Rheumatic Diseases (2014)

To study the association between traditional disease-modifying antirheumatic drugs (c-DMARD) or anti-TNF-α agents and herpes zoster (HZ) in patients with psoriatic arthritis (PsA).A retrospective cohort study was conducted in patients with PsA between 2002 and 2013. Patients were grouped as follows: no DMARDs (Group A); c-DMARDs (Group B); anti-TNF-α agents (Group C); anti-TNF-α agents in combination with c-DMARDs (Group D). Crude incidence rates (IR) were calculated as number of HZ episodes per 1000 patient-years. A Cox regression model was used to adjust for HZ risk factors (age, gender, steroid use, Charlson Comorbidity Index score, and previous treatment) in order to estimate their contribution to the risk of the first HZ event.The study included 3128 patients, mean age 50.26±14.54 years; 46.2% male. During a period of 20 096 person-years 182 HZ events were observed. The crude IR (95% CI) of HZ in the study population was 9.06 per 1000 patient-years, and in Groups A-D 7.36 (5.41 to 9.79), 9.21 (7.5 to 11.21), 8.64 (4.84 to 14.26), 17.86 (10.91 to 27.58), respectively. In a multivariate analysis, age (HR 1.01, 95% CI 1.00 to 1.02), treatment with steroids (HR 1.08, 95% CI 1.04 to 1.13), and a combination of anti-TNF-α agents and c-DMARDs (HR 2.37, 95% CI 1.32 to 4.22) were significantly associated with HZ events.In our database, the risk of HZ was significantly increased with age, treatment with steroids, and combination of anti-TNF-α agents and c-DMARDs, but not with c-DMARDs or anti-TNF-α therapy alone. Time to HZ event was shorter in patients treated with anti -TNF-α agents.
Ontological significance of the dream world
Authors: Gordon Globus
Journal: Behavioral and Brain Sciences (2013)

Abstract Sometimes while sleeping we find ourselves thrown amidst an authentic, albeit bizarre, world. The process of integration by means of which memory elements might be fabricated into a seamless world indistinguishable from the world of waking life is not explained by Llewellyn, who focuses instead on the elaborative encoding of memories. Ontological implications of the sometimes indiscernibility of wake and dream worlds are considered.
IFN-γ Inhibits Gastric Carcinogenesis by Inducing Epithelial Cell Autophagy and T-Cell Apoptosis
Authors: Shui Ping Tu, Michael Quante, Govind Bhagat, Shigeo Takaishi, Guanglin Cui, Xiang Dong Yang, Sureshkumar Muthuplani, Wataru Shibata, James G. Fox, D. Mark Pritchard, Timothy C. Wang
Journal: Cancer Research (2011)

Abstract IFN-γ mediates responses to bacterial infection and autoimmune disease, but it is also an important tumor suppressor. It is upregulated in the gastric mucosa by chronic Helicobacter infection; however, whether it plays a positive or negative role in inflammation-associated gastric carcinogenesis is unexplored. To study this question, we generated an H+/K+-ATPase-IFN-γ transgenic mouse that overexpresses murine IFN-γ in the stomach mucosa. In contrast to the expected proinflammatory role during infection, we found that IFN-γ overexpression failed to induce gastritis and instead inhibited gastric carcinogenesis induced by interleukin-1beta (IL-1β) and/or Helicobacter infection. Helper T cell (Th) 1 and Th17 immune responses were inhibited by IFN-γ through Fas induction and apoptosis in CD4 T cells. IFN-γ also induced autophagy in gastric epithelial cells through increased expression of Beclin-1. Finally, in the gastric epithelium, IFN-γ also inhibited IL-1β- and Helicobacter-induced epithelial apoptosis, proliferation, and Dckl1+ cell expansion. Taken together, our results suggest that IFN-γ coordinately inhibits bacterial infection and carcinogenesis in the gastric mucosa by suppressing putative gastric progenitor cell expansion and reducing epithelial cell apoptosis via induction of an autophagic program. Cancer Res; 71(12); 4247–59. ©2011 AACR.
Translation of Near-Infrared Fluorescence Imaging Technologies: Emerging Clinical Applications
Authors: E.M. Sevick-Muraca
Journal: Annual Review of Medicine (2011)

Technical developments in near-infrared fluorescence (NIRF) imaging and tomography have enabled recent translation into investigational human studies. Noninvasive imaging of the lymphatic vasculature for diagnosis and assessment of function has been uniquely accomplished with NIR using indocyanine green (ICG), a nonspecific dye that has comparatively poor fluorescent properties compared to emerging dyes. Adjunct use of NIRF-ICG for (a) intraoperative sentinel lymph node mapping for cancer staging, (b) video-angiography during surgery, and (c) discrimination of malignant from benign breast lesions detected by mammography and ultrasongraphy also evidences the clinical utility of NIRF. Future NIRF imaging agents that consist of bright fluorescent dyes conjugated to disease-targeting moieties promise molecular imaging and image-guided surgery. In this review, emerging NIRF imaging is described within the context of nuclear imaging technologies that remain the "gold standard" of molecular imaging.
Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study
Authors: R Fleischmann, J Vencovsky, R F van Vollenhoven, D Borenstein, J Box, G Coteur, N Goel, H-P Brezinschek, A Innes, V Strand
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Background:</h3> Tumour necrosis factor α (TNFα) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Treatment with TNFα inhibitors reduces disease activity and improves outcomes for patients with RA. This study evaluated the efficacy and safety of certolizumab pegol 400 mg, a novel, poly-(ethylene glycol) (PEG)ylated, Fc-free TNFα inhibitor, as monotherapy in patients with active RA. <h3>Methods:</h3> In this 24-week, multicentre, randomised, double-blind, placebo-controlled study, 220 patients previously failing ⩾1 disease-modifying antirheumatic drug (DMARD) were randomised 1:1 to receive subcutaneous certolizumab pegol 400 mg (n = 111) or placebo (n = 109) every 4 weeks. The primary endpoint was 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50/70 response, ACR component scores, 28-joint Disease Activity Score Erythrocyte Sedimentation Rate 3 (DAS28(ESR)3), patient-reported outcomes (including physical function, health-related quality of life (HRQoL), pain and fatigue) and safety. <h3>Results:</h3> At week 24, the ACR20 response rates were 45.5% for certolizumab pegol 400 mg every 4 weeks vs 9.3% for placebo (p&lt;0.001). Differences for certolizumab pegol vs placebo in the ACR20 response were statistically significant as early as week 1 through to week 24 (p&lt;0.001). Significant improvements in ACR50, ACR components, DAS28(ESR)3 and all patient-reported outcomes were also observed early with certolizumab pegol and were sustained throughout the study. Most adverse events were mild or moderate and no deaths or cases of tuberculosis were reported. <h3>Conclusions:</h3> Treatment with certolizumab pegol 400 mg monotherapy every 4 weeks effectively reduced the signs and symptoms of active RA in patients previously failing ⩾1 DMARD compared with placebo, and demonstrated an acceptable safety profile. <h3>Trial registration number:</h3> NCT00548834.
Learning to Live With Missing Quality-of-Life Data in Advanced-Stage Disease Trials
Authors: Gary W. Donaldson, Carol M. Moinpour
Journal: Journal of Clinical Oncology (2005)

In advanced-stage disease, palliation can be the most important objective. Quality-of-life (QoL) outcomes provide an intuitively reasonable way to monitor palliation from the patient’s perspective. However, patients with advanced-stage disease are often unable to complete a series of QoL assessments because of deteriorating health. This introduces a possible bias in a clinical trial because patients who are healthy enough to complete the assessments may not represent the target population. In this issue, Brown et al report QoL outcomes from a non–small-cell lung cancer trial comparing supportive care regimens with and without chemotherapy. The analysis of completers only was based on half the baseline sample, and the proportion of completers differed by treatment arms. Despite comprehensive descriptions of the missing data problems and sensitivity analyses designed to cope with them, considerable uncertainty remains. Uncertainty is inevitable with this degree of missing data, but a few key questions can both sharpen focus and suggest practical steps to limit the impact of missing data.
Selective Exclusion of High Titer Donor Plasma and Immunoadsorption Chromatography As Steps to Reduce Isoagglutinin Titers in IVIG
Authors: Liane Hoefferer, Ibrahim El Menyawi, Brigitte Siani, Martin Imboden, Annette Gaida, Isabelle Glauser, Reinhard Bolli, Katharina Willimann, Sandra Wymann, A. Adriano Marques, Eleanora Widmer
Journal: Journal of Allergy and Clinical Immunology (2015)
Treatment of Cancer by the Method of Revici
Authors: David Lyall
Journal: JAMA (1965)

A Clinical Appraisal Group was organized in January 1963, for the purpose of evaluating the treatment of cancer by the method of Emanuel Revici, MD. Dr. Revici, a native of Rumania, emigrated to Paris in 1936, to Mexico in 1941, and to the United States in 1947. Engaging in research and clinical activities in these various places, he developed his theories of the cause and the treatment of disease. A number of papers were written in the foreign and American literature. These culminated in a book<sup>1</sup>published in 1961 to which the reader is referred for additional details. Since 1955, his activities have been carried out in three geographically separate units, all in New York City: Trafalgar Hospital, the Institute of Applied Biology, and a basic science laboratory. Generous support has been given by a number of organizations and groups. It appears that over the years a sum in
<i>KIT</i> Gene Mutations and Copy Number in Melanoma Subtypes
Authors: Carol Beadling, Erick Jacobson-Dunlop, F. Stephen Hodi, Claudia Le, Andrea Warrick, Janice Patterson, Ajia Town, Amy Harlow, Frank Cruz, Sharl Azar, Brian P. Rubin, Susan Muller, Rob West, Michael C. Heinrich, Christopher L. Corless
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We recently identified a KIT exon 11 mutation in an anorectal melanoma of a patient who had an excellent response to treatment with imatinib. To determine the frequency of KIT mutations across melanoma subtypes, we surveyed a large series of tumors. Experimental Design: One hundred eighty-nine melanomas were screened for mutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. A subset of cases was evaluated for BRAF and NRAS mutations. Immunohistochemistry was done to assess KIT (CD117) expression. Results: KIT mutations were detected in 23% (3 of 13) of acral melanomas, 15.6% (7 of 45) of mucosal melanomas, 7.7% (1 of 13) of conjunctival melanomas, 1.7% (1 of 58) of cutaneous melanomas, and 0% (0 of 60) of choroidal melanomas. Almost all the KIT mutations were of the type predicted to be imatinib sensitive. There was no overlap with NRAS mutations (11.1% of acral and 24.3% of mucosal tumors) or with BRAF mutations (absent in mucosal tumors). Increased KIT copy number was detected in 27.3% (3 of 11) of acral and 26.3% (10 of 38) of mucosal melanomas, but was less common among cutaneous (6.7%; 3 of 45), conjunctival (7.1%; 1 of 14), and choroidal melanomas (0 of 28). CD117 expression, present in 39% of 105 tumors representing all melanoma types, did not correlate with either KIT mutation status or KIT copy number. Conclusions: Our findings confirm that KIT mutations are most common in acral and mucosal melanomas but do not necessarily correlate with KIT copy number or CD117 expression. Screening for KIT mutations may open up new treatment options for melanoma patients.
Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria
Authors: Macé M. Schuurmans, Francine Hoffmann, Raija L. Lindberg, Urs A. Meyer
Journal: Hepatology (2001)

Zinc mesoporphyrin (ZnMP) is a potent inhibitor of heme oxygenase (HO) and represses 5–aminolevulinic acid synthase (ALAS). These properties make it a potential candidate for treatment of inducible acute hepatic porphyrias, diseases characterized by neurovisceral symptoms, and massive ALAS induction. Effects of intraperitoneal ZnMP (2.5–10 μmol/kg/d) and heme arginate (3–6 mg/kg/d) on plasma levels of 5–aminolevulinic acid (ALA), on messenger RNA (mRNA), and activity of hepatic ALAS and HO were studied in porphobilinogen deaminase-deficient mice treated with phenobarbital (100 mg/kg/d) to induce ALAS. ZnMP (5 μmol/kg/d) led to a significant reduction of plasma ALA levels to 31% of controls ( P &lt; .01) by lowering the activity of hepatic mitochondrial and cytosolic ALAS to 29% and 25% of controls, respectively ( P &lt; .03). ZnMP decreased the mRNA levels of hepatic ALAS to 53% ( P &lt; .03) of controls and this repression was more pronounced than that achieved with heme arginate. In contrast to heme arginate, ZnMP led to a significant reduction of HO activity. We conclude that the combined effect of ZnMP on highly induced ALAS and on HO may be of potential benefit for human acute hepatic porphyrias and therefore merits further in vivo investigations addressing questions raised by this study. (Hepatology 2001;33:1217–1222.)
Older Women With Breast Cancer: Slow Progress, Great Opportunity, Now Is the Time
Authors: Hyman B. Muss, Jan Busby-Whitehead
Journal: Journal of Clinical Oncology (2011)

visits for patients treated for localized primary cutaneous melanoma. J Clin Oncol 29:4641-4646, 2011 4. Siegel R, Ward E, Brawley O, et al: Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212-236, 2011 5. Romano E, Scordo M, Dusza SW, et al: Site and timing of first relapse in stage III melanoma patients: Implications for follow-up guidelines. J Clin Oncol 28:3042-3047, 2010